Newer, unconventional treatment methods may better manage breast cancer side effects in the future


Breast cancer treatments are often linked to an array of potential side effects – some of which could be considered debilitating – but researchers continue to investigate new strategies to mitigate these toxicities.

Previous research has shown that gabapentin, which is used to treat seizures and nerve pain, and Zyprexa (olanzapine), an antipsychotic medication, may be beneficial in managing pain and hot flashes that may result from treatment for breast cancer.

However, current research aims to evaluate some newer, unconventional treatment methods to reduce the effects of chemotherapy-induced neutropenia and vaginal dryness.

Dr. Charles L. Loprinzi, a consultant in the Division of Medical Oncology in the Department of Oncology at the Mayo Clinic in Rochester, Minnesota, has conducted more than 100 clinical trials evaluating ways to control symptoms in cancer patients.

“Symptom control research is about trying to prevent, treat and better understand the symptoms caused by cancer and the treatment of cancer,” Loprinzi said in an interview with CURE® sister publication OncologyLive.®. “Breast cancer patients can (experience side effects) because of the treatments we give them or the disease itself.”

For example, breast cancer patients frequently receive chemotherapy, which can lead to chronic nausea, vomiting, and neuropathy (numbness and tingling). Additionally, patients receiving hormone therapy may experience hot flushes and pain, and those undergoing surgery or radiation therapy affecting the lymph nodes may develop lymphedema (a buildup of fluid in the soft tissues of the body).

The decision to stop treatment due to side effects can be controversial, and research regarding best practices is in its infancy, according to Loprinzi.

However, the development of strategies that do not include the use of estrogen to manage chemotherapy-induced hot flashes in breast cancer patients is something Loprinzi can talk about, having participated in about 30 clinical trials on the subject throughout his career and now as the principal investigator of an ongoing phase 3 trial. The study is evaluating lower doses of oxybutynin in patients who are not candidates or uninterested in hormone replacement therapy, with the aim of determining whether the lower dose results in fewer side effects than doses higher.

Prior to her presentation at the 39th Annual Breast Cancer Conference in Miami, Loprinzi shared some of the most common treatment-related toxicities in breast cancer and provided an overview of the various current and experimental approaches available to patients.

Question: What are common side effects in the context of breast cancer and how are they typically managed?

To respond: Hot flashes are sometimes caused by the treatments we give to breast cancer patients. Sometimes it’s because we deny them the use of estrogen because we’re afraid of what estrogen might do to (the) breast cancer. For this reason, finding ways to inhibit and treat hot flashes in patients without using estrogen has been a big topic (of discussion) over the past 15-20 years. We found a number of non-hormonal agents (as treatment options), such as antidepressants and others (gabapentinoids), oxybutynin, and progesterone-like hormones.

Another common problem for breast cancer patients, which can be a long-standing problem, are the (side effects) of aromatase inhibitor (AI) medications. (These) drugs can cause aches and pains that are going to be significant, and they can cause many patients to want or stop the drugs. (However, data from) randomized, placebo-controlled trials (have shown) that acupuncture may be helpful. There is also some evidence that exercise and (Cymbalta; duloxetine, a drug commonly used for anxiety and depression) may be helpful.

The other way to think about dealing with these (side effects) is (to switch) to a different drug (in addition to) AIs, (like) tamoxifen, which doesn’t have this problem. (Clinicians have to) decide what benefit they (they) are trying to get from this medicine and whether it is worth continuing the treatment if the patient experiences a lot (of side effects).

What can be done for some of the common side effects of chemotherapy?

Chemotherapy-induced neuropathy (is common). Many chemotherapy drugs can cause numbness, tingling, and pain, which can be problematic when patients take these drugs and can limit the amount patients can take. (Unfortunately,) when you stop the drugs, the effects can linger for months or years afterwards and can lead to patients having more falls (and) getting injured and inhibiting their quality of life for a long time. We want to give chemotherapy the best chance of beating cancer, but sometimes that judgment has to be made if the help it gives (the patient) is outweighed by the toxicity caused by the treatment. Sometimes stopping therapy early may be the right answer, even if it’s something we don’t necessarily want to do.

To date, we have nothing that has been shown to help prevent this problem other than not administering or reducing the dose of chemotherapy. That said, one promising area is the use of cryotherapy when patients are receiving chemotherapy. We know that when we put ice caps on patients’ scalps, it decreases blood flow (and) decreases metabolism, and patients might (experience) less hair loss when we go this route. (The same kind of thought process can also be true) for hands or feet. We don’t have proof of benefit yet, but there is a big push to do a clinical trial, which hopefully can answer that question. An aid (comes with the addition of) (Cymbalta), which can be helpful in diminishing the effects; it doesn’t work very well, but it is (an option).

Another (main concern for me) is the nausea and vomiting when we give chemotherapy. Over the decades we have had different treatments that are not helpful in reducing them. However, in recent years (Zyprexa; olanzapine), which is an antipsychotic type drug, has come on the scene, and we have been able to show that it is useful in reducing nausea and vomiting, and it is (since ) became established in the context (of breast cancer). There is also relatively new information that the drug (Zyprexa) may be useful in patients with advanced cancers who are not receiving chemotherapy or radiation therapy. Often they are patients in the last weeks or months of their life, and they may have a lot of problems with nausea and vomiting due to cancer or other drugs they (receive). There is data that olanzapine in this setting can decrease nausea and vomiting and stimulate appetite.

What research has the potential to improve the future of toxicity management in breast cancer care?

There is a big effort with cryotherapy, and we are well advanced in discussions with the (National Cancer Institute [NCI] to start a trial) that will randomize patients who receive neurotoxic type chemotherapy (like) paclitaxel to cryotherapy (vs standard of care). The group that developed Paxman hair caps to decrease alopecia (working to reduce chemotherapy-induced peripheral neuropathy) using a machine (placed on) the hands and feet. The cold (from the machine is supplied) in a regulated way like the scalp (technology) and can also cause some compression too.

Data on why the process works (shows) that it decreases blood flow to that area when there’s a lot of chemotherapy going on, and there’s data (shows) if you apply some compression there- low, using tight surgical gloves, which was the easy way to do this, you get some compression that might be helpful.

Vaginal dryness (is another disease) which can create a big problem for patients during menopause. It’s more problematic in breast cancer patients because some of the treatments we give (like) AIs lower estrogen. Estrogen keeps the vagina relatively healthy, and when you lower estrogen it can cause vaginal dryness and pain during sex. There is an approach called laser therapy where an instrument is placed in the vagina and gives small pulses of laser, which can cause irritation to the vaginal wall (but can) cause the vaginal wall to recur more to become thicker and better along this line. This protocol has been approved by the NCI and (the trial investigators) will randomize patients with this condition to get vaginal laser treatment versus non-laser vaginal treatment. The randomized trial (aim of the) is to help determine if this is a useful approach for patients. Whether (laser treatment is) beneficial or may cause more (side effects) than it is worth has been controversial over the years.

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