Pilot study of duloxetine for treatment of aromatase inhibitor-associated musculoskeletal symptoms

Breast Oncology Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
Cancer (Impact Factor: 4.89). 12/2011; 117(24):5469-75. DOI: 10.1002/cncr.26230
Source: PubMed


Approximately 50% of postmenopausal women with hormone receptor-positive early stage breast cancer treated with an aromatase inhibitor (AI) develop musculoskeletal symptoms. Standard analgesics are relatively ineffective. Duloxetine is a serotonin norepinephrine reuptake inhibitor with proven efficacy for treatment of multiple chronic pain states. The authors investigated the hypothesis that duloxetine is efficacious for treatment of AI-associated musculoskeletal symptoms.
The authors performed a single-arm, open-label phase 2 study of duloxetine in postmenopausal women with breast cancer who developed new or worsening pain after treatment with an AI for at least 2 weeks. Patients were treated with duloxetine for 8 weeks (30 mg for 7 days, then 60 mg daily). The primary endpoint was a 30% decrease in average pain score over 8 weeks, and secondary outcomes included change in average and worst pain, pain interference, depression, sleep quality, and hot flashes. Statistical analysis was done with t tests for paired data.
Twenty-one of 29 evaluable patients (72.4%) achieved at least a 30% decrease in average pain, and 18 of 23 patients (78.3%) who completed protocol-directed treatment continued duloxetine. The mean percentage reduction in average pain severity between baseline and 8 weeks was 60.9% (95% confidence interval [CI], 48.6%-73.1%), and in maximum pain severity it was 59.9% (95% CI, 47.0-72.7%). The most common adverse events were grade 1 or 2 fatigue, xerostomia, nausea, and headache.
Duloxetine appears to be effective and well tolerated for treatment of AI-associated musculoskeletal symptoms. Future randomized, placebo-controlled studies are warranted.

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Available from: Max S Wicha, Jan 04, 2015
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    • "Effective management of AIMSS is still a mystery in clinical practice, as the mechanisms behind AIMSS are not clearly understood. A number of small interventional trials investigating acupuncture [19,20], vitamin D [18], glucosamine [21], short-term low-dose prednisolone [22], thymosin α1 [23], duloxetine [24] and yoga [25] have provided various treatment strategies. However, most of these trials have had some methodological and practical limitations, including small sample sizes, larger-than-anticipated drop-out, a single-center design, lack of control group and blinding, and a short follow-up period. "
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    ABSTRACT: Background Aromatase inhibitors (AIs) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. One of the main adverse effects of AIs is musculoskeletal symptoms, which leads to a lower quality of life and poor adherence to AI treatment. To date, no effective management of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) has been developed. Methods/design To determine whether the traditional Chinese medicine Yi Shen Jian Gu granules could effectively manage AIMSS we will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial. Patients experiencing musculoskeletal symptoms after taking AIs will be enrolled and treated with traditional Chinese medicine or placebo for 12 weeks. The primary outcome measures include Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis Index, and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands, which will be obtained at baseline and at 4, 8, 12 and 24 weeks. Discussion The results of this study will provide a new strategy to help relieve AIMSS. Trial registration ISCTN: ISRCTN06129599 (assigned 14 August 2013).
    Full-text · Article · May 2014 · Trials
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    • "Diuretics were recently reported to reduce arthralgia symptoms in a retrospective study consistent with the finding of joint effusion and fluid in the tendon sheaths [90]. Duloxetine, a serotonin and norepinephrine reuptake inhibitor, was shown to significantly reduce AI-associated pain in a single-arm, open-label phase II study and improved functional status [101]. Other antidepressants and anti-convulsants are often used in the treatment of chronic pain disorders; however, their use has not been evaluated in AI-induced arthralgia. "
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    ABSTRACT: Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskeletal side effects are substantial and often lead to discontinuation of therapy. Ideally, the symptoms should be prevented or adequately treated. This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including osteoporosis, fractures, and arthralgias. Recent advances have been made in identifying potential mechanisms underlying these effects. Adequate management of symptoms may enhance patient adherence to therapy, thereby improving breast cancer-related outcomes.
    Preview · Article · Mar 2011 · Breast cancer research: BCR

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