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First ASCO survivor care guidelines tackle fatigue, anxiety/depression, neuropathy

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Not effective means of preventing or alleviating symptoms, but outlines what is known

ASCO has reported three new guidelines related to survivorship care, involving anxiety and depression symptoms in patients with cancer; cancer-associated fatigue; and prevention and/or treatment of chemotherapy-induced neuropathy.


Dr. Charles L Loprinzi

In the first, dealing with anxiety and depression, ASCO did not start from scratch but instead utilized Pan-Canadian practice guidelines on screening, assessment, and care of psychosocial distress in patients with cancer, recommending that patients be evaluated for depression and anxiety symptoms during and following treatment. ASCO also recommends that practitioners identify resources available in their practices for treating these disorders. Noting that patients do not often comply with follow-up recommendations for treatment of depression and anxiety symptoms, the guidelines additionally suggest that patients be reassessed routinely.

In its guidelines for managing fatigue in adult patients with cancer, ASCO again chose to rely on previously developed Pan-Canadian guidelines that it supplemented with two National Comprehensive Cancer Network Clinical Practice Guidelines, one on fatigue and another on cancer survivorship. These ASCO guidelines recommend that providers intermittently assess patients for fatigue, and that the cause of the fatigue be evaluated with an appropriate history and physical examination – including, if appropriate, follow-up with selected screening laboratory evaluations. They also recommend that patients receive counseling. As far as interventions for treating cancer-related fatigue (assuming that other contributing factors such as pain, depression, and sleep disturbances have been treated appropriately), they most strongly recommend physical activity. In terms of pharmacological interventions, these guidelines suggest that there is some evidence, albeit limited, that psychostimulant/wakefulness agents, such as methylphenidate and modafinil, might provide some benefit. They also note that preliminary data support that ginseng and vitamin D show some promising effects, but need to be further evaluated.

The ASCO guidelines regarding chemotherapy-induced neuropathy did not rely on earlier guidelines, as none exist that relate to this issue. The authors extensively reviewed the literature for agents that had been tested as potential ways to prevent chemotherapy-induced neuropathy. Despite a large number of drugs evaluated, none of them, to date, has been proven effective in this regard. The guidelines support duloxetine as the best agent to use in practice, based on a recent positive placebo-controlled clinical trial, and list additional treatment options that, while lacking in strong evidence, are worth considering, including gabapentin/pregabalin; tricyclic antidepressants; and a topical formulation of baclofen, amitriptyline, and ketamine.

These three new ASCO supportive-care guidelines address three prominent symptoms for cancer survivors and, while there are not, at this time, very effective means for preventing or alleviating these symptoms, they do set the stage for what is currently known. Hopefully, future updates of these guidelines will be able to identify more effective means of managing these important symptoms.

Dr. Charles L. Loprinzi is professor of oncology at the Mayo Clinic Cancer Center, Rochester, Minn. He served on the ASCO panel that developed the chemotherapy-induced peripheral neuropathy guideline, and has received research funding from Pfizer and Competitive Technologies.


 

The American Society of Clinical Oncology has issued three new practice guidelines related to fatigue; anxiety and depression; and chemotherapy-induced peripheral neuropathy in patients with cancer.

For fatigue, the guideline emphasizes regular screening, treatment of treatable contributing factors, and nonpharmacological interventions such as exercise and cognitive behavioral therapy, allowing for the use of psychostimulants in some patients. For depression and anxiety, the guidelines name no favored medications or regimens but stress identification of at-risk patients through regular screening, along with careful referral to treatment. The guidelines recommend duloxetine to treat chemotherapy-induced peripheral neuropathy.

The guidelines represent the first of what ASCO says is a continuing series on survivorship care. The organization cited the growing importance of managing late treatment and cancer-related effects, as cancer survivors are expected to reach 18 million in the United States by 2022, an increase of nearly 4 million from 2012.

ASCO’s anxiety and depression guideline (doi: 10.1200/JCO.2013.52.4611) derives largely from a Pan-Canadian practice guideline. For its guideline on fatigue in survivors (doi: 10.1200/JCO.2013.53.4495), ASCO integrated recommendations from existing Pan-Canadian guidelines, along with guidelines published by the National Comprehensive Cancer Network. ASCO’s guideline on chemotherapy-induced peripheral neuropathy (CIPN) is original (doi: 10.1200/JCO.2013.54.0914).

The CIPN guideline is based on a review of 48 randomized controlled trials of interventions designed to prevent or alleviate CIPN, which is "relatively distinct from other forms of neuropathic pain in many ways, including pathophysiology and symptomatology," the guideline authors noted, and affects nearly 40% of patients treated with multiple agents.

The new guideline does not recommended any agents for the prevention of CIPN, and rejects a host of agents used in other forms of neuropathic pain – including acetyl-l-carnitine, amifostine, amitriptyline, nimodipine, and vitamin E, among others – for treating established CIPN. Venlafaxine is not recommended either, though "data support its potential utility," the guideline authors acknowledged, saying that further evidence was needed. "The identification of new agents to prevent and/or treat CIPN is essential," they wrote.

Only duloxetine, also used in patients with diabetic neuropathy, is recommended for CIPN. Duloxetine may work better for oxaliplatin-induced, as opposed to paclitaxel-induced, painful neuropathy, the guideline noted, adding that more studies were necessary to confirm this.

ASCO cited three other options as acceptable to try, despite limited evidence, in patients with CIPN: a tricyclic antidepressant such as nortriptyline; gabapentin or pregabalin; and a compounded topical gel made containing baclofen, amitriptyline HCl, and ketamine. But the guideline authors stopped short of making formal recommendations for any of these, citing unproven benefit.

The fatigue guideline promotes a program of physical activity after cancer treatment, also recommending cognitive behavioral therapy and other psychosocial interventions. Yoga and other mind-body interventions are sanctioned, and the stimulant wakefulness agents modafinil and methylphenidate are given cautious recommendation with the caveat that there is limited evidence for their use in patients who have completed treatment and are disease free.

The anxiety and depression guideline stresses that all patients with cancer and who have completed treatment be evaluated regularly for symptoms of depression and anxiety, using validated measures, throughout the trajectory of care. Clinicians are asked to identify the resources available in their communities to treat these disorders.

Four of the CIPN guideline authors, Robert Dworkin, Bryan Schneider, Ellen M. Lavoie Smith, and Charles L. Loprinzi, disclosed receiving compensation or research funding from biomedical or pharmaceutical firms. Of the fatigue guideline authors, Carmelita P. Escalante, Patricia A. Ganz, Gary Lyman, and Paul Jacobsen disclosed research support. None of the depression and anxiety guideline authors disclosed conflicts of interest.

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