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

Abstract

Purpose: Bone pain is a common side effect of pegfilgrastim and can interfere with quality of life and treatment adherence. This study investigated the impact of antihistamine prophylaxis on pegfilgrastim-induced bone pain.

Methods: This is a two-stage enrichment trial design. Patients receiving an initial dose of pegfilgrastim after chemotherapy were enrolled into the observation (OBS) stage. Those who developed significant back or leg bone pain (SP) were enrolled into the treatment (TRT) stage and randomized to daily loratadine 10 mg or placebo for 7 days. SP was defined by Brief Pain Inventory as back or leg pain score ≥5 and a 2-point increase after pegfilgrastim. The primary end point of TRT was reduction of worst back or leg bone pain with loratadine, defined as a 2-point decrease after treatment compared to OBS.

Results: Two hundred thirteen patients were included in the final analysis. Incidence of SP was 30.5 %. The SP subset had a worse overall Functional Assessment of Cancer Therapy-Bone Pain score (33.9 vs. 51.7, p < 0.001) and a higher mean white blood cell count (15.4 vs. 8.4 K/cm(3), p = 0.013) following pegfilgrastim than those without SP. Forty-six patients were randomized in the TRT. Benefit was 77.3 % with loratadine and 62.5 % with placebo (p = 0.35). Baseline NSAID use was documented in four patients (18.2 %) in loratadine arm and two patients (8.3 %) in placebo arm, with baseline non-NSAID use documented in five (22.7 %) and six (25 %) patients, respectively. Eight additional patients used NSAIDS by day 8 compared to day 1 (six in the loratadine and two in the placebo arm). A total of six additional patients used non-NSAIDS by day 8 compared to day 1 (four in the loratadine and two in the placebo arm).

Conclusions: Administration of prophylactic loratadine does not decrease the incidence of severe bone pain or improve quality of life in a high-risk patient population. ClinicalTrials.gov identifier: NCT01311336.

Keywords: Antihistamine; Bone pain; Loratadine; Pegfilgrastim; Prophylaxis; Taxane.

Conflict of interest statement

The authors declare that they have no conflict of interest or financial relationship with the organization that sponsored the research. The authors have had full control of all primary data, and agree to allow the journal to review their data if requested.

Figures

Figure 1. CONSORT

a Significant Pain (SP) was defined as a worst back/leg pain score ≥5 by day 8 post chemotherapy and a 2 point increase during the 7 days after pegfilgrastim use, using the Worst Pain Scale (0-10) of the Brief Pain Inventory b Stratification by taxane administration c 3 participants were incorrectly stratified by taxane use

Figure 2

Severity of bone pain before (day 1) and after (day 8) pegfilgrastim administration during OBS†. † Observation Stage

Figure 3

Site of Pain at Day 8 of OBS† according to Pain Significance (per protocol definition) * Fisher exact test, p