Amifostine-related fever-rash during fractionated radiotherapy: diagnostic and predictive role of C-reactive protein.
BACKGROUND
Fever/rash is a side-effect of amifostine that demands immediate interruption of the drug. Here, we focus on the role of C-reactive protein (CRP) as a putative marker linked with amifostine fever/rash.


METHODS
The CRP serum values were analyzed in 496 patients receiving radiotherapy supported with amifostine (500-1000 mg/d). CRP levels were recorded before the onset of radiotherapy (day 0), on day 15 and when the fever/rash appeared. For 121 out of 496 patients, CRP values on day 7 were also available. About 79 patients (15.9%) developed fever/rash symptoms.


RESULTS
The CRP levels before the onset of therapy were 0 to 20.7 mg/dL (normal, ≤0.5 mg/dL). For patients who did not develop fever/rash, the CRP levels increased from a median of 0.30 to 0.50 on day 15; P = 0.001. Patients who developed fever/rash showed a more than 7-fold increase of the median CRP levels (median, 3.50; P < 0.0001). This sharp CRP rise was specific for amifostine-related fever/rash. Initially abnormal CRP levels were linked with a 2-fold risk for fever/rash (P = 0.01), while abnormal levels on day 7 were linked with a 3-fold higher risk (P = 0.08). The occurrence of fever/rash was independent of the amifostine dose level.


CONCLUSIONS
Sharp rise of CRP levels on the day after the fever/rash development suggest amifostine-related etiology of fever/rash. Abnormal initial CRP levels and/or high CRP levels on day 7 should be considered as an alert signal as the probability to develop fever/rash reaches the 30%.
Koukourakis
Michael I
MI
Department of Radiotherapy/Oncology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
Pitsiava
Dimitra
D
Giatromanolaki
Alexandra
A
Kambouromiti
Georgia
G
Sivridis
Efthimios
E
Kartalis
George
G
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D005334:Fever / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000009:adverse effects*; D011878:Radiotherapy / Q000379:methods*
D015415:Biomarkers; D011837:Radiation-Protective Agents; D002097:C-Reactive Protein; D004999:Amifostine