Abstract
Background: Mild-to-moderate bone pain is the most commonly reported adverse event (AE) associated with pegfilgrastim. Anecdotal reports and some studies have suggested that naproxen (an NSAID) and loratadine (an antihistamine) may help reduce bone pain, and both agents are widely used in the clinic for this purpose. Data from prospective clinical trials on the efficacy of these interventions are limited. Methods: In this open-label study (NCT01712009), women ≥18 years of age with newly diagnosed stage I-III breast cancer and ECOG performance status ≤2 who were planning ≥4 cycles of adjuvant or neoadjuvant chemotherapy with pegfilgrastim support starting in cycle 1 were randomized 1:1:1 to receive prophylactic naproxen, prophylactic loratadine, or no prophylaxis to prevent bone pain. Patients who were randomized to the active treatment arms received naproxen (500 mg twice daily) or loratadine (10 mg once daily) for 5 days beginning on the day of pegfilgrastim administration in each of the first 4 chemotherapy cycles. Pegfilgrastim (6 mg) was administered once per cycle, 24-72 hours after chemotherapy. The primary endpoint of the study was all-grade bone pain in cycle 1 from AE reporting. Secondary endpoints included bone pain in cycles 2-4 and across all cycles from AE reporting and various measures of patient-reported bone pain by cycle and across all cycles. Results: Six hundred patients were enrolled. Race: white 83.0%, black or African American 14.1%, Asian 1.2%. Mean (SD) age: 54.2 (11.1) years. Stage I/II/III: 25.6%/50.1%/24.4%. The percentage of patients with all-grade bone pain in cycle 1 from AE reporting was lower in the naproxen and loratadine arms than in the no prophylaxis arm, but these differences were not statistically significant. Mean, maximum, and AUC for patient-reported bone pain were lower in the naproxen and loratadine arms than in the no prophylaxis arm, and some of these differences were statistically significant (no multiplicity correction). Loratadine was associated with fewer AEs than naproxen, and fewer patients discontinued loratadine. See table for additional results. Conclusions: Levels of all-grade bone pain from AE reporting were comparable in the naproxen, loratadine, and no prophylaxis groups, but there was a consistent trend toward lower pain with naproxen and loratadine, particularly when analyzing measures of patient-reported pain. Loratadine was better tolerated than naproxen. Recommendations: Given its ease of administration, tolerability, and potential benefit, treatment with daily loratadine to help prevent bone pain should be considered for patients receiving chemotherapy and pegfilgrastim.
