Abstract
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.
Highlights
Epidemiology studies indicated that lung cancer was the most diagnosed malignant carcinoma word wide and the leading cause of cancer-related deaths for males and second for females [1]
Pre-chemotherapy serum Hcy appeared to correlate with haematological toxicity and may be a useful biomarker for predicting severity of pemetrexed induced haematological toxicity
We found that the serum Hcy levels were correlated with pemetrexed haematological toxicity, including leucopenia, neutropenia and thrombocytopenia, in accordance with the conclusion of Cao et al [22]
Summary
Epidemiology studies indicated that lung cancer was the most diagnosed malignant carcinoma word wide and the leading cause of cancer-related deaths for males and second for females [1]. Several prospective randomized clinical trials demonstrated that overall survival (OS) and disease-free survival (DFS) could be improved for lung adenocarcinoma patients who received pemetrexed chemotherapy regimen as first-line treatment [4,5,6,7]. Haematological toxicities such as leucopenia, neutropenia and thrombocytopenia were common and limited its clinical application. 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
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