Skin rash is a common adverse event associated with
erlotinib therapy. In severe conditions, the
rash could affect patients' QOL. If the
rash occurrence can be predicted,
erlotinib treatment failures can be prevented. We designed an in vivo study that applied
erlotinib regimens resembling its clinical application to evaluate possible
erlotinib-induced
skin rash biomarkers for humans and simultaneously observe the effects of
erlotinib discontinuation, followed with or without
dose reduction, on
rash development. Rats were divided into four groups: placebo, constant (
erlotinib 35 mg/kg on d1-d21), intermittent (
erlotinib 70 mg/kg on d1-d7 and d15-d21), and mimic (
erlotinib 70 mg/kg on d1-d7 and
erlotinib 35 mg/kg on d15-d21). Blood sampling was performed on d1, d8, d15, and d22. The samples were used to measure
erlotinib concentrations, the level of hepatic and renal function
markers, immune cell percentages, and immune cells' CD45 expression levels.
Erlotinib 70 mg/kg generated high mean circulating
erlotinib concentrations (>1800 ng/mL) that led to severe rashes.
Erlotinib dose reduction following
rash occurrence reduced circulating
erlotinib concentration and
rash severity. After the treatment, the escalation of neutrophil percentages and reduction of neutrophils' CD45 expression levels were observed, which were significantly correlated with the
rash occurrence. This study is the first to show that
erlotinib-induced
skin rash may be affected by the reduction of neutrophils' CD45 expression levels, and this is a valuable finding to elucidate the
erlotinib-induced
skin rash formation mechanism.