Intravenous Voriconazole (IV-VORI) Prevents Invasive Fungal Infections (IFI) in Patients (pts) with Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS).

Background: IFI is the most frequent cause of mortality in pts with AML and MDS undergoing chemotherapy. None of the antifungal prophylactic regimens used since 1992 at MD Anderson Cancer Center appeared to be significantly superior in the prevention of IFI.

Study Aims: To compare the efficacy and safety of IV-VORI versus IV-ITRA as antifungal prophylaxis in AML and MDS pts receiving chemotherapy

Patients and Methods: Pts older than 18 years old receiving induction or salvage chemotherapy, without documentation of prior IFI were eligible. Pts were randomized on day 1 of chemotherapy to receive IV-VORI 400 mg q12 h x 2 days followed by 300 MG IV twice per day or IV-ITRA 200 mg q12 h x 2 days followed by 200 mg IV once per day. Prophylaxis continue until recovery from neutropenia, developed possible/proven IFI, complete remission, declared resistant or up to 35 days for induction pts and up to 42 days for salvage pts.

Results: 114 pts were evaluable (49 on IV-ITRA, 65 on IV-VORI). Baseline characteristics were similar in both groups. 102 were induction pts and 12 were on first salvage. Median time on prophylaxis was 21 (induction) and 17 days (salvage) for both groups. 45% pts on IV-ITRA and 48% pts on IV-VORI completed prophylaxis without modification (p=ns). Two pts on IV-ITRA developed IFI (1 disseminated C. glabrata and 1 disseminated Fusarium) as oppose to none on the IV-VORI arm (p=0.101). No significant differences were seen in the number of pts that required empiric antifungal therapy due to persistent fever or possible fungal pneumonia (14% on IV-VORI, 18% on IV-ITRA). 15/49 pts on IV-VORI (23%) versus 4/49 (8%) on IV-ITRA discontinued prophylaxis due to side effects (p=0.036). Reversible increase in the liver function tests (9 on IV-VORI, 4 on IV-ITRA) and hallucinations (5 on IV-VORI) were the most frequent adverse events. Response to induction chemotherapy, overall induction mortality and survival were similar in both groups.

Conclusions: 1) IV-VORI appears to be more efficacious than IV-ITRA in preventing IFI in AML and MDS pts receiving chemotherapy. More pts are needed to confirm this finding. 2) IV-VORI tends to be more toxic than IV-ITRA. The usage of high dose IV-VORI may explain the incidence of side effects.