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Long-Term Nerve Damage Possible after Chemotherapy for Breast Cancer

September 19, 2017, by NCI Staff

Credit: iStock

Many women who receive taxane-based chemotherapy to treat breast cancer experience long-term peripheral neuropathy, according to follow-up data from a large clinical trial.

Two years after the start of treatment, more than 40% of participants in the trial said they still experienced numbness and tingling in their hands or feet, and 10% rated their symptoms as severe. Patients with severe neuropathy reported lower quality of life than patients without severe symptoms.

“We want to ensure that patients understand both the benefits and harms of treatment, but typically they’re only told about the acute side effects,” said the study's senior author, Patricia Ganz, M.D., of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. “Patients can be really surprised when they’re left with lingering neuropathy, or pain, fatigue, cognitive difficulties…[potentially] a whole bunch of stuff that no one’s really prepared them for.”

“It’s now expected that with early-stage breast cancer—or even stage II or III—you’re going to live a long time,” added Ann O’Mara, Ph.D., head of Palliative Research in NCI’s Division of Cancer Prevention. “So it’s now rising to our attention that we need to be more aware of these chronic toxicities,” she said.

The study was published August 24 in the Journal of the National Cancer Institute.

Lingering Effects of Cancer Treatment

Women enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-30 had breast cancer that could be removed with surgery but were deemed at high risk of recurrence because cancer cells had spread to nearby lymph nodes.

The trial’s main goal was to compare overall survival in women randomly assigned to one of three different chemotherapy regimens containing docetaxel, a type of taxane. Peripheral neuropathy is a common side effect of taxane chemotherapy.

Women in the trial were randomly assigned to receive doxorubicin and docetaxel at the same time; doxorubicin, cyclophosphamide, and docetaxel at the same time (ACT); or doxorubicin and cyclophosphamide at the same time followed by docetaxel (AC→T). Participants in the AC→T group received the highest doses of the taxane in the trial.

Information on neuropathy was collected from patients before treatment, during the fourth cycle of chemotherapy, and at 6, 12, 18, and 24 months after treatment initiation.

In the trial’s main analysis, patients who received AC→T had the best overall survival measured 8 years after the start of therapy, with ACT coming in second. Women who received only doxorubicin and docetaxel had slightly worse survival than women who received either three-drug combination.

By 6 months after treatment initiation, neuropathy rates had increased in all patients, but patients who received docetaxel after the other two drugs had particularly high rates of neuropathy.

Although the percentage of patients in this treatment group who reported experiencing neuropathy symptoms dropped to just under 50% at 24 months after starting treatment, neuropathy rates in this group remained higher than in the other two groups.

Percentage of Trial Participants Who Reported Any Neuropathy
doxorubicin + docetaxel doxorubicin + cyclophosphamide + docetaxel (ACT) doxorubicin + cyclophosphamide followed by docetaxel (AC→T)
* Neuropathy can also be associated with common medical conditions, such as diabetes, or other medical procedures, including some types of surgery.
Before treatment* 19.1% 20.7% 15.8%
At 6-month follow-up 33.3% 37.7% 68.2%
At 12-month follow-up 31.2% 37.1% 56.4%
At 24-month follow-up 34.7% 41.4% 49.8%

Taking Risk Factors for Neuropathy into Account

The researchers found that several patient characteristics increased the risk of lingering neuropathy 24 months after treatment initiation: the presence of neuropathy before treatment; older age; being overweight or obese; having a mastectomy; and a greater number of lymph nodes containing cancer cells.

Because patients treated outside clinical trials are often older and less healthy than patients who enroll in clinical studies, the “real-world” percentage of women who experience chronic neuropathy after taxane-based chemotherapy is likely higher than reported in this study, Dr. Ganz explained.

“Unfortunately, we currently don’t have much to offer patients in terms of treating peripheral neuropathy,” said Dr. O’Mara.

Some patients find limited relief with the drug duloxetine, but the best strategy for now remains trying to prevent neuropathy from occurring in the first place, Dr. Ganz added.

A wide range of chemotherapy regimens are currently endorsed by professional groups for women with breast cancer who are at high risk of recurrence, and choosing one of these regimens over another may result in only a small difference in survival, Dr. Ganz noted. And given that most women will live a long time after treatment, it’s become increasingly important to consider how treatment will impact their future health in initial decisions about therapy, she added.

Recent results from another research team showed that women with chronic neuropathy after cancer treatment were at greater risk for disability and potentially dangerous falls.

In terms of the results from B-30, “I think the important point here is that ACT had almost as much of a survival benefit as AC [followed by docetaxel], but with much less neuropathy. That can be an alternative to choose for a patient who’s at high risk of having neuropathy as a persistent problem,” Dr. Ganz said.

Knowing which patients are at high risk for chronic neuropathy requires oncologists to ask about pre-existing neuropathy before treatment and take other risk factors into account during the initial treatment planning period. However, the time after an initial diagnosis can often be overwhelming for both doctors and patients, so such conversations often don’t happen, she added.

“We need a strategic way in which these [discussions] get incorporated into treatment decision-making,” Dr. Ganz concluded.

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