Pegfilgrastim, which mobilizes white blood cells that fight infection, is indicated by the US Food and Drug Administration for the treatment of cancer patients with nonmyeloid malignancies who are receiving anticancer drugs that are associated with clinically significant febrile neutropenia.1 Although pegfilgrastim is a highly effective drug, about half of the patients who receive it experience moderate to severe bone pain that can interfere with quality of life and compromise adherence to treatment.2 “The mechanism of this bone pain is unclear,” said Joanna Schwartz, PharmD, BCOP, of Albany College of Pharmacy and Health Sciences in Colchester, Vermont, one of the authors of a phase 2 pilot study of loratadine for the prevention of pegfilgrastim-induced bone pain (PIP). Lead author was Julia Moukharskaya, MD, of the University of Vermont College of Medicine in Burlington. Schwartz noted that granulocyte colony-stimulating factor (G-CSF)–induced bone marrow expansion of white blood cell precursors has been associated with histamine release and possibly pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen have not been highly effective in studies of treatment of PIP. Based on anecdotal evidence, the investigators postulated that the antihistamine loratadine could be an effective treatment for PIP. Disappointingly, loratadine failed to have an impact in this phase 2 pilot study. The prospective, randomized, placebo-controlled trial enrolled 227 patients undergoing pegfilgrastim treatment who were observed for the development of clinically significant PIP, which was defined as a score of 5 or higher on the Brief Pain Inventory instrument, with a 2-point or greater increase from baseline after an initial dose of pegfilgrastim. Of these, 65 patients developed PIP and were eligible for randomization, with 45 of them going on to be randomized to loratadine 10 mg or placebo daily for 7 days, initiated on day 1 of pegfilgrastim administration. Twenty patients dropped out of the study because they did not receive further pegfilgrastim, leaving 25 for evaluation (13 in the loratadine group and 12 in the placebo group). Patients randomized to loratadine achieved 59% improvement in PIP from baseline compared with 54.5% for placebo, which was not significantly different. Results remained the same after data were adjusted for use of rescue analgesics, including NSAIDs and non-NSAIDs. “This proves the value of confirming pilot studies. Based on this study, loratadine should not be used to treat PIP. However, a prophylactic study with loratadine versus naproxen use starting the day prior to pegfilgrastim is ongoing, and may guide a future role for this agent in the treatment of PIP,” Schwartz said.
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