Benefit of Early Switch to Liposomal Amphotericin B in Patients with Amphotericin B Deoxycholate-Induced Nephrotoxicity Versus Late Switch.

Amphotericin B deoxycholate (AmBd) nephrotoxicity increases morbidity and mortality however there are no clear guidelines when to switch to liposomal amphotericin B (LAB). We evaluated the benefit of Early Switch (ES) to LAB in patients with AmBd compared to Late Switch (LS).

In this prospective randomized multicenter trial, standard AmBd 1mg/kg/d is initiated in neutropenic patients with haematological malignancies as empirical antifungal therapy (V0). If serum creatinine (SCr) increased of 30% from baseline V0, they were randomized (V1) to LAB 3mg/kg/d (ES) or to pursue AmBd (no switch). In a second step, AmBd treated patients were switched to LAB (LS) if their serum creatinine doubled from V0 or reached a value ≥ 170 μmol/l up to the end of treatment (V2). The analysis included 29 patients [ES=14; no switch=15 with late switch for 9 of them]. Demographics and mean duration of AmBd treatment prior randomization were similar in both groups. Early switch allowed a statistically significant (p=0.04) decrease in serum creatinine (−3.1%) from V1 to V2 as compared with a mean increase of +16.2% in the LS + no switch groups and also demonstrated a significant (p=0.04) increase (+5.1%) in creatinine clearance (ml/min) compared to a decrease (−10.3%) in the LS + no switch groups. This randomised trial demonstrated that an early switch to LAB improves and preserves renal function compared with late switch. Significant reduction of drug-induced nephrotoxicity may impact positively clinical outcomes and provide patients with greater options for chemotherapy treatments.