Serum Homocysteine and Vitamin B12 as Biomarkers for Haematological Toxicity in Lung Adenocarcinoma Treated With Pemetrexed

Abstract

Background Serum homocysteine (Hcy) and vitamin B12 (VitB12) were investigated as serological markers for the prediction of pemetrexed induced haematological toxicity in patients with adenocarcinoma of the lung. Material and Methods A total of 35 lung adenocarcinoma patients who received pemetrexed chemotherapy as first-line treatment were included in the present study. The patients received pemetrexed 500 mg/m2 once every three weeks until disease progression. Serum Hcy and VitB12 levels were analysed prior to chemotherapy. Haematological toxicities (leucopenia, neutropenia and thrombocytopenia) were graded for each cycle of chemotherapy. Serum Hcy and VitB12 concentrations were compared between grades 0-1 and 2-4 haematological toxicity groups. Results A total of 151 chemotherapy cycles were administered to 35 lung adenocarcinoma patients. However, the serum Hcy and VitB12 concentration were only examined and recorded in 61 out of the 151 chemotherapy cycles. For the 61 cycles, grade 2-4 leucopenia, neutropenia and thrombocytopenia were observed in 21, 20 and 10 cases, respectively. Serum Hcy levels were 14.91±4.67 μg/ml, 15.50±4.35 μg/ml and 16.04±4.90 μg/ml for grade 2-4 leucopenia, neutropenia and thrombocytopenia, respectively, which were significantly higher than those of grade 0-1 groups (p<0.05). However, serum VitB12 were not statistically different between grade 0-1 and 2-4 haematological toxicity groups (p>0.05). The area under the ROC curve (AUC) were 0.73 (0.58-0.88), 0.80 (0.66-0.94), 0.75 (0.57-0.93) for serum Hcy and 0.65 (0.50-0.79), 0.64 (0.49-0.78), 0.68 (0.49-0.87) for serum VitB12 as predictive biomarkers of grade 2-4 leucopenia, neutropenia and thrombocytopenia, respectively. Conclusion Pre-chemotherapy serum Hcy appeared to correlate with haematological toxicity and may be a useful biomarker for predicting severity of pemetrexed induced haematological toxicity.

Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis

“…Pemetrexed is a multitarget antimetabolic chemotherapeutic drug [30]. Scagliotti et al [21] first reported the efficacy of cisplatin + pemetrexed compared with cisplatin + gemcitabine regimen in the first-line treatment of advanced NSCLC.…”