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

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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/cm3, 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.

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Acknowledgments

We want to remember Dr. Steven Grunberg, who was a key original investigator in the conception and drafting of the study design and protocol before his untimely passing in 2013. His leadership and vision in the field of supportive care in cancer has been an inspiration to all investigators who participated in this study and the broader oncology community in Northern New England.

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Authors and Affiliations

  1. Harold Alfond Center for Cancer Care, Maine General Health, Augusta, ME, USA

    J. Moukharskaya

  2. Hematology/Oncology, Harrison Health Partners, Poulsbo, WA, USA

    D. M. Abrams

  3. Medical Biostatistics, University of Vermont, Burlington, VT, USA

    T. Ashikaga

  4. University of Vermont Cancer Center, Burlington, VT, USA

    F. Khan, K. Wilson, C. Verschraegen & S. Ades

  5. Albany College of Pharmacy and Health Sciences, Vermont Campus, Colchester, VT, USA

    J. Schwartz

  6. Eastern Maine Medical Center Cancer Care of Maine, Bangor, ME, USA

    T. Openshaw

  7. Central Vermont Medical Center, Barre, VT, USA

    J. Valentine

  8. York Hospital Oncology and Infusion Center, York, ME, USA

    J. Eneman

  9. Champlain Valley Hematology Oncology, Colchester, VT, USA

    P. Unger

  10. Division of Hematology and Oncology, Department of Medicine, University of Vermont Cancer Center, Given Building, E214C, 89 Beaumont Ave, Burlington, VT, USA

    S. Ades

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  1. J. Moukharskaya
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  12. S. Ades
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Corresponding author

Correspondence to S. Ades.

Ethics declarations

All procedures were in accordance with the ethical standards of the local institutional review board and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Each participant signed an IRB-approved, protocol-specific informed consent in accordance with federal and institutional guidelines.

Conflict of interest

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.

Support

This project was supported by Award Number 2U10CA037447 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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Moukharskaya, J., Abrams, D.M., Ashikaga, T. et al. Randomized phase II study of loratadine for the prevention of bone pain caused by pegfilgrastim. Support Care Cancer 24, 3085–3093 (2016). https://doi.org/10.1007/s00520-016-3119-0

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  • DOI: https://doi.org/10.1007/s00520-016-3119-0

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