Dynamics of neutrophil and C-reactive protein reflect the clinical course of pyrexia during combination therapy with dabrafenib and trametinib.

Dynamics of neutrophil and C-reactive protein reflect the clinical course of pyrexia during combination therapy with dabrafenib and trametinib.

Publication date: Jun 10, 2019

Pyrexia is the most common adverse event in patients with melanoma or other solid organ malignancies that are treated with the combination of dabrafenib and trametinib (combi-DT). Given the expanded indication for combi-DT, management of pyrexia is a high priority. No previous case series has revealed which blood markers reflect the course of pyrexia and there is no consensus on the management strategy for pyrexia. The current case series study describes the utility of neutrophil count (NC), neutrophil ratio (NR) and C-reactive protein (CRP) in 11 patients with metastatic melanoma and BRAF V600 mutations who experienced pyrexia during combi-DT in our department. We also described the clinical course of pyrexia episodes that were managed with the concomitant use of oral prednisolone and immediate withdrawal of combi-DT. Consequently, the analysis of 37 pyrexia episodes in 11 patients showed that the differences in NC, NR and CRP at the onset of pyrexia were significantly different from those at pyretolysis (P = 0.01, 0.006 and 0.03, respectively). Additionally, in the 24 pyrexia episodes treated with the concomitant use of oral prednisolone and the immediate withdrawal of combi-DT, the mean duration of pyrexia and the mean time to restart combi-DT were 3 and 6 days, respectively. Therefore, the blood markers that reflect the course of pyrexia during combi-DT may be helpful for the appropriate management of pyrexia; also, our management strategy for pyrexia successfully reduced the duration of pyrexia and did not require a long-term drug holiday. Further large-scale studies are required to verify our results.

Maeda, T., Yoshino, K., Yamashita, C., Nagai, K., Oaku, S., Kato, M., Hiura, A., Uehara, J., and Fujisawa, Y. Dynamics of neutrophil and C-reactive protein reflect the clinical course of pyrexia during combination therapy with dabrafenib and trametinib. 22927. 2019 J Dermatol.

Concepts Keywords
Adverse Event Medicine
Blood Clinical medicine
BRAF Chemical compounds
Combination Therapy Event melanoma
Department Cancer treatments
Malignancies RTT
Melanoma B-Raf inhibitor
Neutrophil Sulfonamides
Organ Dabrafenib
Prednisolone Thiazoles
Pyrexia Trametinib
Fever
Melanoma

Semantics

Type Source Name
gene UNIPROT BRAF
gene UNIPROT CRP
gene UNIPROT CSRP1
disease MESH malignancies
pathway BSID Melanoma
disease MESH melanoma
disease DOID melanoma
drug DRUGBANK Trametinib
drug DRUGBANK Dabrafenib
gene UNIPROT LARGE1
drug DRUGBANK Prednisolone

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