Personalized medicine has been hailed as one of the latest big ideas when treating patients. According to the National Cancer Institute Glossary it’s defined as a “form of medicine that uses information about a person’s own genes or proteins to prevent, diagnose or treat disease.”
What’s missing from the personalized medicine definition and practice?
The goal of treating early stage breast cancer is to obliterate cancer in the body and keep it from coming back. In metastatic breast cancer (MBC), the goal is to be on a therapy as long as possible to control the disease while maintaining quality of life. With two distinct goals, you’d think there would be two dosing strategies. One is a sprint, and one is a marathon.
Most FDA approvals for cancer drugs include a maximum tolerated dose (MTD) with at least two lower doses that can be used. All three are shown to be effective, otherwise they wouldn’t have been approved.
The National Comprehensive Cancer Network (NCCN) guidelines list the MTD for most of the approved breast cancer therapies for both early stage and metastatic breast cancer. These guidelines are used by many oncologists to determine dosage.
So instead of personalizing the dose to patients based on drug sensitivities in the past, whether the therapy is for disease control or disease elimination, a standard MTD is administered.
In July 2019, I attended an update on breast cancer therapies for oncologists where I was the only advocate present. During an optional lunch session sponsored by a drug company touting their new drug that I’ll call Drug X, I publicly suggested that we aren’t properly dosing new cancer meds when there is no difference in outcomes between maximum tolerated doses and stepdown recommended dose reductions in MBC. Pharma reps swooped in on me after the session.
The reps explained that all patients need to start at MTD because if we don’t start there, we will never know if the patient can tolerate the maximum dose.
Alarms went off in my head. It made no sense to me.
So, let’s say you are a patient with MBC and you’ve been on a few lines of therapy. You have progression and Drug X is your next option. Even if you have low blood counts, have experienced eventual stepdown doses on your other therapies due to sensitivities or side effects, you are to start at the MTD. Why? Because that’s what the guidelines say.
Does this sound right to you?
It doesn’t make sense to me. Why subject a patient to the highest dose when it’s extremely unlikely they will be able to tolerate it and will likely experience serious or reduced quality of life side effects? And, these side effects may reduce the amount of time the MBC patient can safely remain on the drug.
Furthermore, clinical trials are often quick to establish dose standards without taking time to consider a variety of dosing schedules and amounts. Sometimes it takes a few years for oncologists to see their patients experience intolerable side effects at the MTD before they change their personal practice using reduced dosing. That happened with capecitabine.
It seems to me that NCCN guidelines should suggest starting at the lowest dose and ramping up if needed or starting at the middle dose and going up or down based on patient reaction. Some oncologists are already doing this, but outside of guidelines. After all, they are “guidelines” not commandments. Yet oncologists may feel uneasy prescribing outside of these guidelines.
If you are starting a new line of therapy or are on a therapy but experience intolerable side effects, talk to your oncologist about reduced dosing. Your oncologist should be able to explain a good rationale whether to stay at current dose or step down to a lower dose. Make sure you understand the pros and cons. Then it’s your decision how you’d like to proceed.
Adding individualized dosing to the definition of personalized medicine should be the standard of care.
*The opinions expressed are those of the author.
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