Reported Bone Pain in Patients with Breast Cancer Receiving Taxane-Based Chemotherapy in Clinical Trials of Pegfilgrastim.

Abstract

Abstract Background: The most commonly reported adverse event associated with administration of granulocyte colony-stimulating factors (G-CSFs) is mild to moderate bone pain. It has been suggested (but not uniformly accepted) that bone pain associated with pegfilgrastim treatment occurs at a higher frequency, is more severe and less predictable than bone pain associated with filgrastim treatment. This retrospective analysis examined bone pain in patients with breast cancer receiving chemotherapy in pegfilgrastim clinical trials.Methods: Data analyzed are from 3 sponsor-supported trials of once per chemotherapy cycle pegfilgrastim (6 mg fixed dose or 30, 60, or 100 mcg/kg) or daily filgrastim (5 mcg/kg) administered 24 hours after taxane-containing chemotherapy in patients with breast cancer (Holmes et al Ann Oncol 2002;13:903; Holmes et al JCO 2002;20:727; Green et al Ann Oncol 2003;14:29). The adverse events reported in the 3 studies were recoded using MedDRA dictionary and the preferred terms considered bone pain were determined prior to the analysis. Incidence of any grade and grade 3/4 bone pain was determined by treatment (pegfilgrastim or filgrastim) and cycle.Results: Patients receiving pegfilgrastim (n = 356) or filgrastim (n = 252) were included in the analysis. In the 3 breast cancer studies included in this analysis, the proportions of patients who had metastatic disease at study entry ranged from 19% to 48%. The overall incidence of any grade bone pain was 65.7% and 67.9% in the pegfilgrastim and filgrastim arms, respectively (Table). In both treatment arms, bone pain incidence was highest in the first cycle of chemotherapy and decreased in subsequent cycles. Grade 3/4 bone pain was infrequently reported in these studies. PegfilgrastimFilgrastim n = 356n = 252Female, n (%)354 (99.4)250 (99.2)White, n (%)289 (81.2)213 (84.5)Age, mean years (min, max)51 (23, 81)52 (27, 83)Bone pain (any grade), % (95% CI) All cycles65.7 (60.5, 70.7)67.9 (61.7, 73.6)Cycle 146.1 (40.8, 51.4)52.8 (46.4, 59.1)Cycle 230.1 (25.3, 35.3)30.4 (24.7, 36.5)Cycle 325.7 (21.1, 30.7)29.5 (23.9, 35.7)Cycle 423.4 (19.0, 28.3)25.9 (20.5, 32.0)Grade 3/4 bone pain, % (95% CI) All cycles4.8 (2.8, 7.5)6.7 (4.0, 10.6)Cycle 12.8 (1.4, 5.1)4.4 (2.2, 7.7)Cycle 20.9 (0.2, 2.5)0.8 (0.1, 2.9)Cycle 31.2 (0.3, 3.0)2.0 (0.7, 4.7)Cycle 40.6 (0.1, 2.2)1.3 (0.3, 3.6)CI = Confidence intervalConclusions: Bone pain incidence was similar for the pegfilgrastim and filgrastim arms. Bone pain of any grade was common in these breast cancer patients receiving taxane-containing chemotherapy with growth factor support. Bone pain may be associated with a combination of disease state (including metastatic site), co-morbid conditions (eg, arthritis), chemotherapy, and growth factor use. Severe bone pain can occur; however, this was infrequently reported in these patients. In both treatment arms, bone pain incidence was most frequent in the first cycle of chemotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1117.