Thrombogenicity of intravenous 5‐fluorouracil alone or in combination with cisplatin

Acute myocardial infarction was observed in two patients receiving standard intravenous doses of 5‐fluorouracil (5‐FU)‐based chemotherapy. Therefore, the authors prospectively assessed the thrombogenicity of this agent by studying ten patients, six with head and neck cancer and four with gastrointestinal malignancies, receiving 5‐FU (1 g/m²/day) as a constant intravenous infusion over a 4‐day or 5‐day period. The six patients with head and neck cancer also received a single dose of 100 mg/m² of cisplatin on day 1. Blood samples were obtained preinfusion, 24 hours into the infusion, and postinfusion. Samples were assayed for fibrinopeptide A (FpA) by enzyme‐linked immunoassay, for protein C activity (PCa) using a chromogenic substrate (Spectrozyme PCa), and protein C (PCag) and free protein S antigen (PSag) by electroimmunoassay. No patient experienced a thrombotic event. A significant increase was observed in FpA levels during the infusion which returned toward baseline at the conclusion of the infusion. After infusion of 5‐FU, the PCa value was significantly lower than the PCag (37 ± 17 versus 69 ± 24%; P <0.002). No effect on protein S was observed. The changes in the patients receiving 5‐FU alone were comparable to those who also received CDDP. The authors conclude that during the infusion of 5‐FU, the rise in FpA activation and reduction in PCa as compared to PCag are compatible with activation of coagulation.