Duloxetine May Help Relieve AI-Related Musculoskeletal Side Effects

Early-stage breast cancer patients who experience arthralgia symptoms during aromatase inhibitor therapy may benefit from duloxetine treatment

medwireNews: Phase III trial findings suggest that the serotonin–norepinephrine reuptake inhibitor duloxetine may reduce aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) in postmenopausal women with early-stage breast cancer.

“Considering the high incidence of bothersome and intolerable musculoskeletal toxicity in AI-treated women, as well as the paucity of interventions with proven benefit, this trial provides important findings about a new treatment option for women with AIMSS”, the investigators say.

The study included patients who had developed or experienced worsening arthralgia after beginning anastrazole, exemestane or letrozole therapy, with an average joint pain score of at least 4 on a 10-point scale, explain N Lynn Henry, from the University of Utah in Salt Lake City, USA, and co-workers.

In all, 127 patients were randomly assigned to receive duloxetine 30 mg/day for 1 week, followed by a 60 mg/day dose for 11 weeks and 1 week of tapering off medication.

These patients achieved a 0.82-point greater reduction in the average joint pain score on the Brief Pain Inventory at 12 weeks compared with the 128 patients who were assigned to receive placebo, a significant difference after adjusting for stratification factors including baseline pain score and history of taxane use.

In addition, greater improvements with duloxetine versus placebo were seen at 12 weeks for worst pain score and pain interference score on the Brief Pain Inventory. This was also true for outcomes on a functioning pain and stiffness score for knees and hips; a modified score for assessment of function, pain and stiffness of the hands; functional quality of life; and global rating of change scores for pain and stiffness.

Indeed, there was a significant reduction in pain with duloxetine at each 2-week assessment over the 12-week study period, although this difference had disappeared 12 weeks after treatment was completed.

“This finding demonstrates that a short course of therapy does not result in a sustained improvement in symptoms and that continued treatment may be required for management of AIMSS”, the investigators comment in the Journal of Clinical Oncology.

However, duloxetine-treated patients did experience higher rates of any-grade side effects (78 vs 50%) and of grade 3 events (9 vs 4%) than controls, with the most common symptoms associated with the agent being fatigue, nausea, dry mouth and headache. Fatigue, dry mouth and headache were also the most common events in the placebo arm. There were no grade 4 or 5 events.

“It will be important to identify predictors of response to therapy to minimize the number of patients unnecessarily exposed to the toxicity of duloxetine therapy”, N Lynn Henry et al remark.

The authors conclude: “These results support consideration of a short course of duloxetine in symptomatic patients to assess improvement in AIMSS and tolerance of duloxetine.

“Identifying ways to control symptoms and increase adherence with AI therapy while maintaining quality of life could lead to improvements in breast cancer disease-related outcomes.”


Henry NL, Unger JM, Schott AF, et al. Randomized, multicentre, placebo-controlled clinical trial of duloxetine versus placebo for aromatase inhibitor-associated arthralgias in early-stage breast cancer: SWOG S1202. J Clin Oncol; Advance online publication 14 November 2017. DOI: 10.1200/JCO.2017.74.6651

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