Managing Neurotoxicity in Advanced Breast Cancer

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Matti Aapro, MD

Matti Aapro, MD

Neurotoxicity in advanced breast cancer is not limited to chemotherapy-induced peripheral neuropathy, according to Matti Aapro, MD, of IMO Clinique de Genolier, Switzerland. Surgery, radiation therapy, and medical therapy can all have detrimental effects on either the central or peripheral nervous system. 

Pain after breast surgery is not uncommon, even 1 year after the procedure. Central nervous system neurotoxicity after medical therapy can manifest in a wide range of clinical syndromes, including complex cognitive impairment—also known as “chemobrain”—which often develops in the adjuvant setting. “We know that our treatments inflict neurotoxicity,” said Dr. Aapro. 

At the European School of Oncology (ESO)–-European Society for Medical Oncology (ESMO) 4th International Consensus Conference for Advanced Breast Cancer (ABC4) in Lisbon, Dr. Aapro led a discussion on the management of neurotoxicity in patients with advanced breast cancer.1 He noted that most of his recommendations come from the ESMO Clinical Practice Guidelines: Supportive and Palliative Care, a set of recommendations based on findings from evidence-based medicine. 

Peripheral Neuropathy Management 

In the peripheral nervous system, chemotherapy-induced peripheral neuropathy is the most frequently observed treatment-induced damage to patients. “Chemotherapy-induced peripheral neuropathy is not only painful but extremely annoying and can be debilitating for some patients,” he said.

Excitement around certain treatments, such as calcium and magnesium for the -treatment of oxaliplatin-induced peripheral neuropathy, has now waned due to further research debunking the efficacy of the treatments. According to Dr. Aapro, “an impressive amount” of agents and procedures have been evaluated to treat or prevent chemotherapy-induced peripheral neuropathy, and though many ideas around effective treatment are still circulated, they have yet to be proven in prospective, randomized, double-blind, and properly conducted trials. However, much has been written and reviewed about which therapies can potentially be offered to patients complaining of painful polyneuropathy. 

Accepted by most experts with a “moderate level of recommendation” is duloxetine at a dosage adapted to each patient. Other treatments he said are “worth a try” include tricyclic antidepressants (eg, nortriptyline or desipramine), as well as gaba-pentin and pregabalin (Lyrica). 

“Very importantly,” he added, “we should never forget that a lot of these relatively minor complaints in the hands and feet, such as tingling, can be helped by another message to the nerves, so you can use topical gels”—containing, for example, baclofen, amitriptyline, and ketamine—to treat these conditions. A simple and inexpensive treatment—topical application of a 1% menthol cream—is also “worth a try,” he said, though it has yet to be proven in randomized trials. 

Assessment of Pain

According to Dr. Aapro, paramount to dealing with neuropathic pain is first determining the type of pain being described by the patient. He recommends following the ESMO Clinical Practice Guidelines for the Assessment and Treatment of Neuropathic Pain. 

First, determine the category of neuropathic pain: allodynia, causalgia, central pain, dysesthesia, hyperesthesia, hyperalgesia, hyperpathia, or paresthesia. Next, utilize assessment and screening tools for neuropathic pain (ie, Neuropathic Pain Scale, Neuropathic Pain Questionnaire) and conduct a clinical assessment. If the pain is determined to be neuropathic, nonopioid and opioid analgesics may be combined with tricyclic antidepressant drugs or anticonvulsants (eg, amitriptyline or gabapentin). Additionally, radiation therapy can be used to treat neuropathic pain due to bone metastases. 

Impact of Pain

“We also must realize there are many reasons and many settings in which patients have pain,” he said. “Sometimes it is not induced by the drugs only, but by the disease and the effects of the treatments the patient has had.” 

The ESMO recommendations on the assessment of patients with pain state that “the assessment of all components of suffering such as psychosocial distress should be considered and evaluated,” he noted.

According to Dr. Aapro, various forms of cancer treatment neurotoxicity have to be taken into account, and “regrettably, their management … is not well codified.” Pain can manifest in any clinical setting, from the neoadjuvant stage to the end of life, and causes run the gamut, including acute procedural pain, iatrogenic pain, suffering related to comorbidities, metastatic pain, end-of-life pain, and pain in survivors. ■

DISCLOSURE: Dr. Aapro reported no onflicts of interest.


1. Aapro M: ESO-ESMO Advanced Breast Cancer 4th International Consensus Conference. Abstract IN23. Presented November 3, 2017.