Serum biomarkers and paracetamol during post-chemotherapy infections

Paracetamol;Febrile Neutropenia;IL-6;IL-8;Biomarkers;Quality of Life

Bowden, Emily Ellen ; Weinkove, Robert ; Filoche, Sara

University of Otago

关键词: Paracetamol;    Febrile Neutropenia;    IL-6;    IL-8;    Biomarkers;    Quality of Life;   

Others  :  https://ourarchive.otago.ac.nz/bitstream/10523/6060/1/BowdenEmilyE2015BBioMedSc%28Hons%29.pdf

美国|英语

来源: Otago University Research Archive

【 摘 要 】

Background:Febrile neutropenia (FN) is a common complication of cancer chemotherapy defined as fever with neutropenia below 1.0 x109 /L. Prompt antibiotic treatment is life-saving. Antipyretics (e.g. paracetamol) are commonly used during antibiotic treatment to reduce temperature and discomfort.A phase II randomised, placebo-controlled double-blinded trial of paracetamol during FN was completed at Wellington Hospital. This study aimed to determine whether paracetamol affects temperature or quality of life (QoL) during FN, and to assess biomarkers as potential secondary endpoints. Methods:Participants received 1g oral paracetamol or placebo six hourly for 42 h. Tympanic temperature was monitored four hourly. Blood was taken 0, 4, 24 and 72 h after FN presentation. In the current study cytokine bead array was used to determine levels of TNF-α, IL-6, IL-8 and IL-10, procalcitonin (PCT) was assessed by ELISA, and C-reactive protein (CRP) using an immunoturbidimetric method. Participants completed the EQ-5D-5L QoL questionnaire daily and the FACT-N questionnaire on day 3.Results:Of 37 enrolled patients, 22 participants developed FN and received at least one dose of paracetamol (n = 13) or placebo (n = 9). Treatment groups had comparable demographics and vital signs at baseline. Per pre-determined criteria, 23% and 33% of patients had successful treatment in the paracetamol and placebo groups respectively (not significant).Peak temperature was significantly lower in paracetamol- than placebo-treated patients on days 1 and 2 (difference 0.7°C and 0.6°C, respectively, p < 0.01 and p = 0.03), but not on day 3. Average daily temperature was also significantly lower in the paracetamol than placebo group. IL-6, IL-8, IL-10 and TNF-α were raised at baseline and/or 4 h and declined thereafter. PCT peaked at 24 h.Presentation and 4 h levels of IL-6, IL-8, IL-10, PCT and TNF-α, as well as 24 h PCT and 72 h IL-8 levels, were associated with adverse outcome. IL-6 was higher in the placebo than paracetamol group at 24 h (p <0.02). QoL scores were worse in the paracetamol group during the first two days of treatment (difference not significant). Conclusions:Paracetamol was an effective antipyretic during FN. Serum biomarkers change during FN, and IL-6 and IL-8 are promising secondary outcome measures for future trials. The adverse impact of paracetamol on QoL scores was unexpected and requires confirmation in a larger study.