A multicenter, randomized, double blind placebo-controlled trial of amoxicillin/clavulanate for the prophylaxis of fever and infection in neutropenic children with cancer.

Aim Of The Study: To evaluate the effectiveness of oral amoxicillin/clavulanate (25 mg/kg every 12 h) for prevention of fever and/or infection in neutropenic children with cancer.

Methods: Multicenter, prospective, randomized, double blind placebo-controlled trial.

Results: In the intention-to-treat analysis, amoxicillin/clavulanate had a 12% benefit increase in terms of reduction in the incidence of febrile or infectious episodes, compared with placebo [44 of 83 (53%) vs.55 of 84 (65%); 95% confidence interval, -28% to +3%; P = 0.101]. This benefit was also associated with a 30% increase in the probability of failure-free survival at Day 15 (P = 0.138). A logistic regression analysis showed the effect of prophylaxis to be relevant, especially in patients with leukemia or lymphoma and in those not receiving hematopoietic growth factors, with 17 and 15% absolute benefit increases (logistic P = 0.014 and 0.034, respectively). Compliance with oral drugs was good, with very few and nonsevere drug-related adverse events.

Conclusions: In this study amoxicillin/clavulanate was associated with a detectable clinical effect in the reduction of fever and infection in neutropenic children with cancer, especially those with acute leukemia and not receiving growth factors; the study was not powered to demonstrate a statistically significant effect in the overall patient population.