Evaluation of Loratadine for Prevention of Pegfilgrastim-Induced Pain

Randomized Phase II Pilot Study of Loratadine for the Prevention of Pain Caused by the Granulocyte Colony Stimulating Factor Pegfilgrastim

The purpose of this study is to determine the incidence of pegfilgrastim-induced back and leg pain and to determine whether the antihistamine loratadine can prevent pegfilgrastim-induced back and leg pain.

Pegfilgrastim is a myeloid growth factor that stimulates neutrophil precursors and can be used to decrease infection risk associated with neutropenia. However pegfilgrastim may induce back and leg pain in 20-50% of patients. No intervention has been consistently successful in treating or preventing this pain.

The exact mechanism of pegfilgrastim-induced pain is unknown but may be related to histamine-mediated inflammation. Several case reports and anecdotal reports have suggested efficacy of antihistamines for this indication.

This study will have two parts. In the first part (Observational Phase), patients receiving pegfilgrastim will be surveyed to document the incidence of significant pegfilgrastim-induced back and leg pain. In the second part (Treatment Phase), patients who previously experienced such pain will be randomized to receive a 7-day course of either the antihistamine loratadine or placebo to determine whether pegfilgrastim-induced back and leg pain can be prevented with this intervention.

Inclusion Criteria:

• histologic or cytologic evidence of malignancy
• scheduled to receive pegfilgrastim with two consecutive cycles of similar chemotherapy with at least a 14 day interval between cycles
• adequate renal function: estimated creatinine clearance > 30 ml/min
• adequate hepatic function: AST, ALT, total bilirubin <= 2.5 x ULN
• age >= 18 years
• performance status 0-3
• able to read and understand English
• signed Informed Consent

Exclusion Criteria:

• history of hypersensitivity or intolerance to antihistamines
• concurrent use of antihistamines other than study medications during or for 2 days prior to the study period except for a single dose of antihistamine as required for administration of chemotherapy or blood transfusion
• concomitant use of amiodarone
• previous use of pegfilgrastim or filgrastim