An evaluation of plasma homocysteine levels and the hematological toxicity of pemetrexed even with folate supplementation.

Abstract

2594 Background:Systemic folic acid and vitamin B12 supplementation is necessary for pemetrexed treatment, because severe toxicities of pemetrexed treatment without folate supplementation were observed in patients who had high levels of plasma homocysteine (Hcy) in early clinical trials. However, it was not examined whether the plasma Hcy levels would still associated with the hematological toxicity of pemetrexed in patients receiving folate supplementation. The purpose of this study was to examine the relationship between the pretreatment plasma Hcy levels after folate supplementation and the hematological toxicity of pemetrexed monotherapy in advanced non-small cell lung cancer (NSCLC). Methods: From June 2009 to September 2010, 52 NSCLC patients received pemetrexed monotherapy (500mg/m2, every 3 weeks) and also received oral folic acid (0.5mg) daily and a vitamin B12 injection (1.0mg) every 9 weeks, beginning 1 to 2 weeks before the first dose and continuing until 3 weeks after the last dose of the study treatment. The plasma Hcy levels before the first dose of pemetrexed were measured. Complete blood cell counts were measured at least once a week during first cycle of pemetrexed monotherapy. The relationship between the plasma Hcy levels and hematological toxicities during the first cycle of pemetrexed monotherapy were evaluated. Results: The patient characteristics were as follows: male/female: 22/30; median age: 65 years (39-79); histology, adeno/large: 51/1; PS, 0/1/2/3: 25/24/2/1. The mean pretreatment plasma Hcy was 9.01μmol/ml (3.8-34.6μmol/ml). The pretreatment plasma Hcy significantly correlated with the nadir of the absolute leukocyte counts (r=-0.315 p=0.023) and the nadir of the absolute thrombocyte counts (r=-0.302 p=0.032). In addition, the pretreatment plasma Hcy significantly correlated with the decline rates of leukocytes (r=+0.351 p=0.012), hemoglobin (r=+0.414 p=0.002) and thrombocytes (r=+0.417 p=0.002). Conclusions: The Plasma Hcy levels are thus considered to be associated with the hematological toxicity of pemetrexed monotherapy even with folate supplementation.