How Much Chemo Do You Really Need?
In 2015, Kate Vieira Pfitzer had recently been diagnosed with metastatic breast cancer and was trying to make it through several rounds of chemotherapy treatment. She wanted to stick with it and have the best chance of controlling the cancer, especially since she was caring for her three sons, the youngest of whom was 7 at the time. But she developed neuropathy (numbness and pain) in her hands and feet as a side effect of the chemo drug Abraxane, which worsened with each infusion.
“It got to the point that I couldn’t pick up a pen or fork or sign my name,” says Vieira Pfitzer, who is now the metastatic breast cancer program director at SHARE Cancer Support. “Walking became incredibly painful.”
She was reluctant to tell her oncologist how bad her neuropathy had become. She assumed that it was an expected part of treatment and didn’t want to come across as a complainer. “I thought I had no choice but to push through,” she says.
Read more of our special series on chemo side effects to learn about ways to make chemo more manageable and about the early-stage breast cancers that no longer even need chemo.
Eventually, after completing nine of the twelve prescribed Abraxane infusions, she had to stop. “The neuropathy was so far gone by then, I just couldn’t take it anymore,” Vieira Pfitzer says.
Later, she learned that reducing her dose of Abraxane weeks earlier could have been a possibility — one that she hadn’t known to ask about.
“People need to know that lowering the dose can be an option,” she says. “In some cases, the drug will still be effective for you, but you’ll have less side effects and can enjoy life a little more.”
Are cancer drug doses sometimes too high?
Treating breast cancer has always involved tradeoffs. The tradeoff with chemotherapy, targeted therapy, and immunotherapy medicines that can kill cancer cells is that they often carry a risk of harsh side effects. Finding the best dose is essential for treatment to be tolerable and effective.
“It can impact disease outcomes in a negative way if you’re on a dose that does not agree with you,” says Maryam Lustberg, MD, MPH, director of the Center for Breast Cancer at Smilow Cancer Hospital and chief of breast medical oncology at Yale Cancer Center. “If you have terrible toxicity with one drug, it can weaken you, delay care, even close the doors for potential future therapies.”
For people who, like Viera Pfitzer, have been diagnosed with metastatic breast cancer (cancer that has spread to other parts of the body), the stakes are especially high. They typically stay in active treatment for the rest of their lives, receiving more cycles of chemo and other cancer drugs over time than a person with early-stage breast cancer would. And they may find themselves repeatedly having to deal with severe side effects at the start of each new treatment, compromising their quality of life.
People diagnosed with early-stage (stage 1, stage II, or stage IIIa) breast cancer usually receive drugs like chemo and targeted therapy for a limited period of time, if at all. But when the dose of a drug they’re taking is too high, they too might develop long-term, debilitating side effects or have to stop taking a drug early.
For decades, clinical trials for chemotherapy and other cancer drugs focused on finding the “maximum tolerated dose” (MTD) — the highest dose that most of the patients in the trial could tolerate. The theory was that higher doses were more effective. Drug approvals are based on the results of those trials, so when new drugs hit the market, the recommended starting dose has usually been based on the MTD. Researchers didn’t necessarily test whether lower doses could work just as well.
Today, to curb side effects, oncologists do in some cases prescribe lower doses, and/or different dosing schedules, than the standard starting ones listed on a drug’s label. These adjusted doses and schedules are usually still within a range that has been shown to effectively control the cancer in clinical trials. But drug toxicity is still a major problem for many people going through treatment.
In a 2020 survey of 1,221 people with metastatic breast cancer, conducted by the nonprofit Patient-Centered Dosing Initiative (PCDI), 86% reported having a bad treatment side effect. Out of those, 20% had visited an emergency room or hospital because of the side effect and 43% missed at least one treatment because of the side effect.
“There will always be some risk of side effects,” says Evanthia Roussos Torres, MD, PhD, a medical oncologist and researcher at the Keck School of Medicine of USC, in Los Angeles, CA. “The question now is: How can we make the side effects liveable and bearable?”
A movement to change dosing approaches
A growing number of patient advocates and doctors have been calling for more research and awareness about when lower doses can offer the same benefits as higher ones, and for more tailoring of doses to individual patients.
The Patient-Centered Dosing Initiative (PCDI), a patient-led organization founded in 2019, is at the forefront of advocating for these changes.
“If a lower dose can be enough to kill the cancer, why take a higher dose, especially when you’re risking side effects that may impact the rest of your life?” says Julia Maués, lead of the PCDI, who was diagnosed with metastatic breast cancer in 2013. “We’re in a very different world now than when we started our organization. People are much more open to the idea of optimizing dosing.”
In recent years, the U.S. Food and Drug Administration (FDA) launched two new initiatives to help reform cancer drug dosing, in part due to the advocacy efforts of the PCDI and other organizations:
Project Optimus, started in 2021, involves the FDA supporting and encouraging drug makers and researchers to study two or more doses of the cancer drugs they’re developing and to get data on when lower doses can be effective.
Project Renewal, started in 2018, updates the labeling of certain cancer drugs that are already on the market and had dosage recommendations that were based on the maximum tolerated dose.
These initiatives have already had concrete results. For example, in 2022, the oral chemo medicine Xeloda (chemical name: capecitabine), which is used to treat metastatic breast cancer, received a labeling update as part of Project Renewal. The label now includes an option for a lower starting dose.
The efforts by the FDA are building on studies conducted by academic researchers. For example, the Xeloda labeling change came about because several studies conducted after the drug was on the market showed that the lower dose offered the same benefits as the higher, standard one, but caused fewer or less severe side effects. Project Renewal helped to translate that data into new labeling.
Some studies have suggested that reduced dosages of other common drugs used to treat breast cancer can be as effective as the standard dosages. These include the chemo drug Abraxane (chemical name: albumin-bound or nab-paclitaxel) and the targeted therapy drugs Trodelvy (chemical name: sacituzumab govitecan-hziy), Kisqali (chemical name: ribociclib), Ibrance (chemical name: palbociclib), Afinitor (chemical name: everolimus), and Verzenio (chemical name abemaciclib).
Research on lower drug doses is part of a broader push in oncology towards investigating treatment “de-escalation” — ways of reducing the intensity or duration of treatment while maintaining good treatment outcomes.
“When we design clinical trials, more often than in the past we’re looking at: what’s the least amount of a drug we can use and achieve the outcome we’re looking for? It’s the reverse of how we used to approach drug development,” says Dr. Roussos Torres.
Changing the conversation about dosing
Experts say that although progress is being made, it will take years to gather the data that’s needed on alternative dosages of existing drugs and of drugs still in development.
“It takes a long time to get the answers we’re looking for — about when it’s safe to decrease doses and de-escalate therapy. Once we do, we’ll roll that into the standard of care,” says Dr. Roussos Torres.
In the meantime, the PCDI’s Maués and other advocates hope people going through breast cancer treatment and their doctors will get more comfortable with discussing different dosing options and ways of mitigating side effects. Surveys done by the PCDI show that the vast majority of oncologists and patients are open to it.
In a 2021 poll of oncologists who treat metastatic breast cancer, 85% said they did not believe that a higher dose of a cancer drug is always more effective than a lower dose and 97% said they would be willing to discuss individualized drug dosing options with their patients.
In a 2020 poll of patients with metastatic breast cancer, 92% said they would be willing to talk to their doctors about dosing options based on their unique situations.
In routine practice, though, conversations about dosing and side effects can be tricky. Patients are sometimes afraid to broach the subject and ask about all their options, especially during appointments that might already be rushed and too brief.
“We need to educate patients that their quality of life is important, it’s good to have open communication with their doctors about their side effects, and there are things their doctors can do to help before taking them off a drug completely,” says Maués.
How to talk with your treatment team about getting the right dose for you
You may want to ask your treatment team about dosing when you’re making decisions about starting a new chemotherapy, targeted therapy, or immunotherapy medicine — or if treatment is causing troublesome side effects.
It can be scary or uncomfortable to talk with your doctor about side effects, especially if you’re afraid of being taken off a drug that is working to control the cancer. But if you don’t talk openly with your treatment team, you might not find out about all your options for easing your side effects, which could include switching to a more tolerable dose or schedule — or to a different treatment altogether. There might be research showing that taking a lower dose of your current medication can be just as effective for you.
If you’re having trouble starting the conversation, consider bringing a friend or family member with you to an appointment with your doctor. They can provide emotional support and advocate for you.
It’s important for you and your doctor to take into account your unique situation when figuring out the right dose of a medication. The PCDI recommends considering:
your goals and wishes
your overall health (including other health conditions you have or had, your age, and your mobility)
your history of side effects from other drugs
your current and past blood count levels
whether the breast cancer is slow- or fast-growing
whether the cancer has spread to the brain or spinal cord
whether you have what’s known as a visceral crisis (the cancer has spread to a soft organ, such as the lungs or liver, and is interfering with the normal function of the organ)
whether you can afford the medication your doctor is considering prescribing and others that might be needed to help ease side effects
whether you have anyone available to help you at home if you have severe side effects
If you develop a challenging side effect from a breast cancer medicine, there are a number of ways your treatment team can help. “We have lots of options to help you feel better if a drug is not agreeing with you,” says Dr. Lustberg. “Drug holidays, dose reductions, and other strategies are all on the table.” The PCDI suggests asking your medical team:
Can you prescribe medication to relieve the side effect(s)?
Can you suggest other ways to ease the side effect(s), such as complementary therapies?
Can you reduce the dose of the medication, while still effectively treating the cancer?
Can you change the treatment schedule/how frequently I receive the medication?
Can you recommend other changes that could help — like switching from the intravenous form of the drug to the oral one, or getting the drug from a different manufacturer?
Could you refer me to a specialist who could address the side effect(s)?
Depending on your individual situation and preferences, you might also want to explore switching to a different medicine, taking a break from treatment, or stopping treatment.
If your oncologist is acting dismissive when you bring up your concerns about side effects or won’t discuss different treatment and dosing options in detail with you, it may be worth getting a second opinion or even switching doctors.
“You should always have a say in how your care is given,” says Dr. Lustberg. “And your oncologist should understand that quality of life is important to you.”
This content is made possible, in part, by AstraZeneca, Gilead, Lilly, and Pfizer.
— Last updated on December 8, 2024 at 2:56 PM