The correlation between the plasma concentration of gemcitabine and short-term efficacy and adverse reactions in patients with advanced squamous cell carcinoma of the lung using liquid chromatography-mass spectrometry

Abstract

Abstract
Background: Worldwide, non-small cell lung cancers have the highest incidence and mortality rates of all cancers. Gemcitabine (2’,2’-difluoro-2’-deoxycytidine or dFdC, C9H11F2N304) is widely used as the first-line chemo-reagent for lung cancer patients whose tumors have been diagnosed to be at an advanced stage and are therefore unresectable.

Objective: The objective of this systematic study was to establish the correlation between the plasma concentration of gemcitabine and short-term clinical efficacy and adverse reactions in patients with advanced squamous cell carcinoma of the lung using liquid chromatography-mass spectrometry.

Material and methods: In total, 53 patients were given the chemotherapy medications, gemcitabine and cisplatin, every 3 weeks. Plasma concentrations of gemcitabine were determined using liquid chromatography-mass spectrometry. A modified methodology of the liquid chromatography-mass spectrometry system was verified and performed to detect plasma concentrations of gemcitabine. The clinical endpoints – short-term clinical efficacy and adverse reactions – were evaluated after two cycles.

Results: The plasma concentration range of gemcitabine in 53 patients was 1.58-28.70μg/ml (mean 14.37±8.63μg/ml), with 28 patients in the >15μg/ml group (mean 21.76±3.45μg/ml), and 25 patients in the ≤15μg/ml group (mean 6.09±3.57μg/ml). The clinical benefit rate (CBR) of the >15μg/ml group was significantly higher than that of the 15μg/ml group (p<0.05). The incidences of leukopenia and neutropenia, thrombocytopenia and grade III-IV gastrointestinal reactions in the >15μg/ml group were significantly higher than in the ≤15μg/ml group (p<0.05). There was no statistical difference between the two groups in terms of the incidences of reduced hemoglobin, liver and kidney function damage, allergic reaction and rash (p>0.05). The analysis of the plasma concentration of gemcitabine and the percentage of reduction in neutrophil count (NEUT) (r2 = 0.3212; p<0.05) and platelet (PLT) (r2 = 0.6439; p<0.05) showed a significant positive correlation.

Conclusions: In patients with advanced non-small cell lung cancer, a high plasma concentration of gemcitabine can improve the short-term clinical efficacy of treatment, but increase the incidence of grade III-IV adverse reactions. [Ethiop. J. Health Dev. 2021; 35(1):72-82]

Key words: Non-small cell lung cancer, gemcitabine, plasma concentration, short-term efficacy, adverse reactions