First-day step-down to oral outpatient treatment versus continued standard treatment in children with cancer and low-risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study

Abstract

Background: The standard treatment of fever in chemotherapy-induced neutropenia (FN) includes emergency hospitalization and empirical intravenous antimicrobial therapy. This study determined if first-day step-down to oral outpatient treatment is not inferior to continued standard regarding safety and efficacy in children with low-risk FN.

Procedure: In a randomized controlled non-blinded multicenter study, pediatric patients with FN after non-myeloablative chemotherapy were reassessed after 8-22 hours of inpatient intravenous antimicrobial therapy. Low-risk patients were randomized to first-day step-down to experimental (outpatient, oral amoxicillin plus ciprofloxacin) versus continued standard treatment. Exact non-inferiority tests were used for safety (no serious medical complication; non-inferiority margin of difference, 3.5%) and efficacy (resolution of infection without recurrence, no modification of antimicrobial therapy, no adverse event; 10%).

Results: In 93 (26%) of 355 potentially eligible FN episodes low-risk criteria were fulfilled, and 62 were randomized, 28 to experimental (1 lost to follow-up) and 34 to standard treatment. In intention-to-treat analyses, non-inferiority was not proven for safety [27 of 27 (100%) vs. 33 of 34 (97%; 1 death) episodes; 95% upper confidence border, 6.7%; P = 0.11], but non-inferiority was proven for efficacy [23 of 27 (85%) vs. 26 of 34 (76%) episodes; 95% upper confidence border, 9.4%; P = 0.045]. Per-protocol analyses confirmed these results.

Conclusions: In children with low-risk FN, the efficacy of first-day step-down to oral antimicrobial therapy with amoxicillin and ciprofloxacin in an outpatient setting was non-inferior to continued hospitalization and intravenous antimicrobial therapy. The safety of this procedure, however, was not assessable with sufficient power.