Moukharskaya J, Abrams D M, Ashikaga T, Khan F, Schwartz J, Wilson K, Verschraegen C, Openshaw T, Valentine J, Eneman J, Unger P, Ades S
Harold Alfond Center for Cancer Care, Maine General Health, Augusta, ME, USA.
Hematology/Oncology, Harrison Health Partners, Poulsbo, WA, USA.
Support Care Cancer. 2016 Jul;24(7):3085-93. doi: 10.1007/s00520-016-3119-0. Epub 2016 Feb 19.
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.
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.
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).
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.
骨痛是培非格司亭常见的副作用，会影响生活质量和治疗依从性。本研究调查了抗组胺药预防对培非格司亭所致骨痛的影响。
这是一项两阶段富集试验设计。化疗后接受初始剂量培非格司亭的患者进入观察（OBS）阶段。出现严重背部或腿部骨痛（SP）的患者进入治疗（TRT）阶段，并随机分为每日服用10毫克氯雷他定或安慰剂，为期7天。SP由简明疼痛量表定义为背部或腿部疼痛评分≥5分且在使用培非格司亭后增加2分。TRT的主要终点是氯雷他定减轻最严重的背部或腿部骨痛，定义为与OBS相比治疗后疼痛评分降低2分。
213例患者纳入最终分析。SP的发生率为30.5%。与无SP的患者相比，SP亚组在使用培非格司亭后癌症治疗功能评估-骨痛总分更差（33.9对51.7，p<0.001），平均白细胞计数更高（15.4对8.4K/cm³，p=0.013）。46例患者在TRT阶段被随机分组。氯雷他定组的获益率为77.3%，安慰剂组为62.5%（p=0.35）。氯雷他定组有4例患者（18.2%）记录有基线非甾体抗炎药使用情况，安慰剂组有2例患者（8.3%）；氯雷他定组有5例患者（22.7%）、安慰剂组有6例患者（25%）记录有基线非非甾体抗炎药使用情况。与第1天相比，到第8天另有8例患者使用了非甾体抗炎药（氯雷他定组6例，安慰剂组2例）。与第1天相比，到第8天另有6例患者使用了非非甾体抗炎药（氯雷他定组4例，安慰剂组2例）。
预防性使用氯雷他定并不能降低高危患者群体中严重骨痛的发生率或改善生活质量。ClinicalTrials.gov标识符：NCT01311336。
