Determining the best dose of a cancer medicine for an individual

Finding the Right Dose

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It’s long been thought that the “right dose” of a cancer medication is the maximum dose that most people receiving the drug can tolerate. This thinking began with chemotherapy and is often extended to other types of cancer drugs.

A group of metastatic breast cancer patient (MBC) advocates is now questioning that paradigm and is urging a new approach that is more attuned to the needs of individuals.

The group conducted a survey to better understand MBC patients’ experiences with the side effects of their medications and their willingness to discuss with their doctors alternative approaches for identifying the best doses for them.

The findings from the survey were presented at this year’s annual meeting of the American Society of Clinical Oncologists.

The Traditional Approach

Dosing for cancer medications has traditionally been based what is known as the “maximum tolerated dose” or MTD. This approach is mainly associated with chemotherapy, where it has long been thought that the optimal dose is the maximum dose a patient can tolerate before side effects become too great.

Early stage clinical trials are typically organized around identifying the MTD. Once this dose is identified, it tends to be carried forward, and becomes the standard dose for the medication once it is approved. The MTD is calibrated based on a patient’s height and weight, but is otherwise standard for all.

This standard dose usually applies for all patients–whether they are early stage patients or individuals with metastatic cancer, most of whom will need to be receiving treatment for cancer for the rest of their lives. Even the newer, targeted cancer therapies are often approved using this approach to dosing, which may not be as relevant since these drugs work differently from chemotherapies.

If a patient is having problems with side effects, their doctor may reduce the dose of the medication or alter the treatment schedule. But most patients start with the standard dose.

A Patient-Centered Approach

A group of patient advocates has founded The Patient-Centered Dosing Initiative, which supports a different approach for patients with MBC–one that focuses on sustaining lives while also optimizing the quality of life. The group is supported by an advisory board of medical oncologists who are accomplished breast cancer researchers.

The advocates point out that there are a number of studies which show that certain therapies for MBC are just as effective at lower doses, with reduced adverse side effects.

The group recognizes that more studies are needed, but encourages individuals with MBC to have conversations with their doctors about dosing criteria before starting treatments. Criteria that can be considered include the patients’ personal goals, age, body mass index (BMI), current and past health situation, history of side effects from other drugs, personal financial situation and availability of in-home care.

Survey Results Presented at ASCO

The group wanted to find out more about MBC patients’ willingness to have discussions with their doctors about dosing for their medications based on their individual situations.

They conducted a survey of MBC patients in 2020, and the results were published in the Journal of Clinical Oncology and were presented by the lead advocate on the project, Anne Loeser, at this year’s ASCO annual meeting.

The survey was distributed through social media channels, online support groups and organization newsletters. During August 2020, a total of 1,221 individuals with MBC completed the survey.

This is what the survey found:

  • 86% of these MBC patients had experienced at least one “bad” side effect from their medications (with “bad” defined by the person completing the survey).
  • As a result of side effects, 20% visited the emergency room or hospital and 43% missed at least one treatment.
  • 98% of those with side effects reported them to their doctors and 82% received assistance with them, most commonly by means of dose reductions and/or prescription medications.
  • 83% of the patients who were given a dose reduction felt better, at least initially.
  • 92% of those surveyed said they would be willing to discuss with their doctors alternative dosing options based on their individual characteristics and preferences.

What Comes Next

After completing the patient survey, the advocates when on to conduct a survey of medical oncologists to better understand their perspectives on the treatment-related side effects of individuals with MBC and how to alleviate them.

The results of the oncologist survey are available on the group’s website. To highlight just a couple of points from that survey:

  • 85% of the oncologists said the standard dose is NOT always more effective than a lower dose.
  • 97% said they would be willing to discuss dosing options with patients in the future based on the patients’ personal attributes.

Moving forward, the advocates want to engage with industry to better tailor dosing to individual patients’ needs.

In her remarks at ASCO, Loeser noted that in a perfect world there would be phase III clinical trials comparing dose levels. As this is not often feasible, instead the advocates want to work with the companies conducting clinical trials to retroactively compare data on outcomes of patients who switched to lower doses because of side effects with those who remained on the MTDs. And they would like to proactively integrate that type of comparison into clinical trial design.

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