Randomized phase II pilot study of loratadine for the prevention of bone pain caused by pegfilgrastim.

9628 Background: Bone pain is a common side-effect of pegfilgrastim and can interfere with a patient’s quality of life and treatment adherence. Antihistamine therapy may have analgesic activity in such patients. This study was designed to investigate the impact of antihistamine loratadine prophylaxis on pegfilgrastim-induced bone pain (PIP). Methods: This is a two stage trial design with the first stage identifying eligible patients who developed significant clinical PIP after receiving an initial dose of pegfilgrastim (6 mg SC) in the chemotherapy setting, and the second stage representing a randomized trial of a 7-day course of loratadine 10 mg daily or placebo starting on day 1 of pegfilgrastim administration. Significant PIP, assessed by Worst Pain Scale (0-10) of the Brief Pain Inventory, was defined as worst pain score >5 and a 2 point increase during the 7 days after pegfilgrastim. The primary end-point of the study was reduction of significant PIP with loratadine, defined as 2 point decrease in worst PIP between treatment and observation stages. Rescue use of other analgesics was allowed. Target sample size was based on the following assumptions: 30% incidence of significant pain, 10% benefit with placebo, 50 % benefit with loratadine, 89% power (chi-square test, 2-sided alpha=0.05) , and stratification by taxane use. Results: A total of 227 patients were enrolled in the observation stage, of whom 213 were included in the final analysis. Incidence of significant PIP was 30.5%. 45 patients with breast, lung and GI malignancy entered the randomization stage, male/female 11 /34, median age 56 (range 31-89). Gender, age, malignancy type, taxane use, and additional use of rescue NSAIDS and non-NSAIDS were all comparably distributed in loratadine vs. placebo groups (p=0.58). The rate of improvement in the significant PIP was 59.1% for loratadine arm and 54.5% for placebo arm (p=1.0). Results were unchanged after adjustment for rescue analgesic use or taxane therapy. Conclusions: Administration of prophylactic loratadine does not decrease the incidence of significant PIP. Clinical trial information: NCT01311336.