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Aromatase Inhibitor-Related Musculoskeletal Problems Characterized; Current Treatments Found Mostly Ineffective

Susman, Ed

doi: 10.1097/01.COT.0000461872.45740.52


SAN ANTONIO—Aromatase inhibitor-related musculoskeletal syndromes—not often mentioned in pivotal clinical trials—affect more than half of women taking the drugs to prevent breast cancer recurrence, according to data reported at the San Antonio Breast Cancer Symposium.

“These symptoms occur frequently and we really have no good therapies for treating these women,” Janine Lombard, MBChB, a specialist consultant in oncology at Calvary Mater Hospital in Australia and lecturer at the University of Newcastle, Australia, said in an interview at her poster study.



The symptoms that are now considered part of the aromatase inhibitor musculoskeletal syndrome include arthritis, arthralgia, myalgia, carpal tunnel syndrome, joint stiffness, and paresthesia. “Arthralgia and other joint-related symptoms are common in menopausal women but are also a significant toxicity of aromatase inhibitors and are the most common cause of treatment discontinuation,” she said.

“In the study, those patients who developed the syndrome typically did so within the first eight weeks of therapy. However, the syndrome may also represent a persistent problem, as symptoms worsen from six to 24 months after starting.”

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Many Treatment Options Tried

Treatment for these symptoms remain suboptimal, she said, and because of that, is also varied. For the study, questionnaires were sent to the Breast Cancer Network Australia Review and Survey Group, with 370 usable responses returned, which detailed the types of therapies used in attempts to mitigate symptoms.

The patients tried over-the-counter medications—most frequently paracetamol (acetaminophen)—as well as various physician-prescribed pharmaceuticals and non-medical treatments as tai chi, with an overall success rate of 27 percent, Lombard said.

Doctors most often prescribed anti-inflammatory agents—to about 22 percent of patients—and these treatments were deemed effective in 13 percent of patients; in another five percent, patients were unsure if the treatment was of any help, and in four percent of the cases patients reported that the drugs were of no help.

Clinicians also prescribed codeine, morphine, vitamin D, corticosteroid injections, prednisone, paracetamol, and other treatments such as bisphosphonates, as well as duloxetine and amitriptyline and other antidepressants.

When patients went to the pharmacy for over-the-counter treatments, their choices were more varied but not much more successful. The first choice in over-the-counter treatment was found to be paracetamol, selected by 47 percent of patients. Thirty percent of these treatments were reported as being effective; patients said they were unsure of the effectiveness in another eight percent; and about 19 percent said there was no impact on reducing the symptoms.

Over-the-counter anti-inflammatory agents worked for about 17 percent of the patients, but six percent said they were unsure of a benefit and seven percent said there was no benefit.

Other over-the-counter medications included fish oil, glucosamine, vitamin D, krill oil, ibuprofen, chondroitin, aspirin, emu oil, magnesium, calcium, rose hips, and a variety of other herbs and/or nutrients.

Among the non-drug interventions tried, massage therapy was felt to be effective in 17 percent of the 24 percent of people who tried it; yoga in 10 percent of the 16 percent of those practicing that; acupuncture in seven percent of the 11 percent of people who tried it; and tai chi in three percent of the 3.5 percent of patients who used that.



Other options tried to even less success were general exercise, physiotherapy, Bowen therapy (a form of hands-on holistic pressure), osteopathy, Feldenkrais (reducing pain through self-awareness), reflexology, and trigger point injections.

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‘Huge Unmet Need’

“There is a huge unmet need for treatment for these musculoskeletal side effects from aromatase inhibitors,” Lombard said. “Women use a number of interventions to manage aromatase inhibitor musculoskeletal syndrome, but their efficacy appears limited.”

These musculoskeletal complaints may have been a major factor in women discontinuing treatments, she noted. About 26 percent of the patients in the study took aromatase inhibitors for less than a year. About 64 percent stayed on the drug for one to five years and 10 percent for more than five years.

A total of 33 percent of the women in the study said they considered stopping aromatase inhibitor therapy because of joint symptoms and 27 did discontinue treatment—and 68 percent of those women reported stopping because of musculoskeletal problems.

When they stopped taking their originally prescribed aromatase inhibitor, about half refused to try another treatment, and about 17 percent switched to tamoxifen.

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Similar in U.S.

Although the study involved women in Australia, the situation is pretty much the same in the United States, said Coy Heldermen, MD, Assistant Professor of Medical Oncology at the University of Florida, Gainesville.

“This is a common problem with my patients,” he told OT while reviewing the poster. “There is a lot of testing and a lot of switching of therapies related to patients with these musculoskeletal problems. Everything that the Australian researchers have described is mirrored in my clinical experience as well,” he said.

“In the early studies of aromatase inhibitors, the problem with musculoskeletal syndrome did not seem to be an issue,” Lombard noted. “We don't know why that is, but in our clinical experience 80 percent of women who discontinue treatment report that this syndrome is a factor.”

Still, she said, many of the symptoms—joint pain, fatigue, genitourinary symptoms, hot flushes, depression, headache, and anxiety—are similar to what 50 percent of menopausal women without breast cancer report as well. So since her patients are informed about what possible adverse events might occur, it could be that they are noting symptoms that may just be related to menopause and not the treatment, Lombard acknowledged. However, most of the women who described the symptoms said they had begun with the onset of treatment or that the complaints worsened when they began treatment with aromatase inhibitors.

Finding an effective treatment is important, because aromatase inhibitors have been shown to have superior efficacy over tamoxifen in disease-free survival and even overall survival, Lombard said. She noted that two thirds of women with early breast cancers have hormone receptor positive disease and, therefore most of them would benefit from at least five years of adjuvant endocrine treatment; and some high-risk patients would receive further benefit from 10 years.

In conducting the survey, the researcher team emailed 2,390 members of Breast Cancer Network Australia in April 2014, seeking information about women who had been diagnosed with early breast cancer, defined as Stage I-III since 2007 and had used aromatase inhibitors in the past or were currently taking the drugs. The 45-question survey included demographics, use of aromatase inhibitors and tamoxifen, clinical manifestations and risk factors for musculoskeletal complaints, reasons for discontinuations and efficacy or intervention used for treatment of symptoms.



There was no response from 75 percent of the requests; and 10 percent of those who did reply failed to meet the study criteria, leaving 15 percent of the responses for analysis. About 81 percent of the patients responding reported musculoskeletal complaints, most often related to the feet (68%); hands or wrists (65%); knees (62%); hips (56%); shoulders or elbows (49%); back (46%); or eck (3%). Many patients reported multiple sites of joint pain.

Lombard did caution, though, that one of the limitations of the study was the small number of responses meant that the numbers in the individual interventions was also small, making it difficult to generalize.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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