No abstract

Purpose Adherence to aromatase inhibitor (AI) therapy for early stage breast cancer is limited by AI-associated musculoskeletal symptoms (AIMSS). Duloxetine is FDA-approved for treatment of multiple chronic pain disorders. We hypothesized that treatment of AIMSS with duloxetine would improve average joint pain compared with placebo. Patients and Methods This randomized, double-blind, phase 3 trial included AI-treated postmenopausal women with early stage breast cancer and who had average joint pain of ≥4/10 that developed or worsened since AI therapy initiation. Patients were randomized 1:1 to duloxetine versus placebo for 13 weeks. The primary endpoint was average joint pain through 12 weeks, examined using multivariable linear mixed models, adjusted for stratification factors (baseline pain score 4–6 vs. 7–10 and prior taxane use). Clinically significant change in average pain was defined as a ≥2-point decrease from baseline. Results Of 299 enrolled patients, 127 duloxetine-treated and 128 placebo-treated patients were evaluable for the primary analysis. Average joint pain was 0.82 points lower for duloxetine-treated patients compared with placebo-treated patients by 12 weeks (95% CI −1.24 to −0.40, p=0.0002). Similar patterns were observed for worst joint pain, joint stiffness, pain interference, and functioning. Rates of adverse events (AEs) of any grade were higher for duloxetine-treated patients (78% vs 50%); grade 3 AEs were similar. Conclusion Treatment with duloxetine for AIMSS was superior to placebo among women with early stage breast cancer, although it resulted in more frequent low grade toxicities.

NCT00936702.

Summary Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life. rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg -1 wk -1 ) in each cohort. Patients were monitored for adverse events, including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up. A dose-response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg -1 wk -1 cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl -1 respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing.