Mihovil Roglić

Erlotinib-related rhabdomyolysis: the role of pharmacogenetics and drug–drug interaction

but is an uncommon complication of antineoplastic treatment [5–8]. However, cases of rhabdomyolysis have been described in patients treated with imatinib and, up to now, only one case in patient treated with erlotinib alone [9, 10]. Erlotinib is mainly metabolized by cytochrome P450 (CYP) 3A4 isoenzyme and is transported across different barriers by P-glycoprotein (MDR1/ABCB1) and ABCG2 drug transporters; the potential for CYPand transportermediated drug–drug interactions (DDIs) is high, especially with CYP3A4, P-glycoprotein (P-gp), and ABCG2 inhibitors. According to in vitro and in vivo studies, erlotinib is not only the substrate but also a P-gp/ABCG2 inhibitor [11, 12]. Interindividual pharmacokinetic variability of erlotinib is affected not only by the genetic heterogeneity of drug targets, but also by patient’s pharmacogenetic background. Published data show higher erlotinib through concentrations at steady state in patients with the ABCB1 1236TT-2677TT-3435TT genotypes compared with other groups. Patients carrying these genotypes had a higher risk of developing high grade 2 toxicity (moderate to severe skin rash and diarrhea) [13].

Cancer-related inflammation as predicting tool for treatment outcome in locally advanced and metastatic non-small cell lung cancer

BACKGROUND Lung cancer is the leading cause of cancer deaths and the non-small cell lung cancer (NSCLC) represents 80% of all cases. In most cases when diagnosed, it is in locally advanced or metastatic stage, when platinum based doublet chemotherapy is the established therapeutic option for majority of the patients. Predictive factors to filter the patients who will benefit the most from the chemotherapy are not clearly defined. Objective of this study was to explore predictive value of pre-treatment C-reactive protein (CRP), fibrinogen and their interaction, for the response to the frontline chemotherapy. METHODS In this retrospective cohort study 170 patients with locally advanced and metastatic NSCLC were included. Relationship between baseline level of CRP and fibrinogen and response to the frontline chemotherapy was assessed. RESULTS We found that pre-treatment CRP and fibrinogen values were statistically significantly correlated. Chemotherapy and CRP, fibrinogen, and their interaction were independently significantly associated with disease control rate at re-evaluation. There was statistically significant difference in median pre-treatment CRP level between the patients with disease control or progression at re-evaluation, 13.8 vs. 30.0 mg/L respectively, P=0.026. By Johnson-Neyman technique we found that in patients with initial fibrinogen value below 3.5 g/L, CRP level was significantly associated with disease control or progression of the disease. Above this fibrinogen value the association of CRP and disease control was lost. CONCLUSIONS The findings from this study support the growing evidence of inflammation and cancer relationship, where elevated pre-treatment level of CRP has negative predictive significance on the NSCLC frontline chemotherapy response.

P11. Efficacy and safety of erlotinib in advanced squamous cell lung cancer

Background Erlotinib is epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor which showed efficacy and tolerability in patients with advanced non-small cell lung cancer (NSCLC), especially in group of patients which harbor activating mutations in EGFR.