Invasive Mycoses in High-Risk Cancer Patients - a Prospective Analysis of Clinical Parameters, Side Effects, Drug Interactions and Costs for the Safe and Economically Appropriate Use of Systemic Antifungal Agents.

Invasive mycoses (IM) show high morbidity and mortality rates among immunocompromised patients (pts). Especially allogeneic stem cell transplant (allo-SCT) recipients and acute leukemia pts under induction chemotherapy are at risk and benefit from early systemic antifungal drug (SAD) interventions. Nevertheless, the increasing use of SADs has led to considerable costs and represents a substantial burden for public health systems. Available SADs differ in their antifungal properties, side effects (SE), potential drug interactions (PDI) and costs. Efficacy and safety profiles of SAD have been derived from clinical trials, which, however, may not reflect ‘everyday clinics' and true SAD efficacy due to tight inclusion and exclusion study criteria. Aim of our analysis was to prevent SAD application errors and to assure their economically appropriate use.

Since 11/06, we prospectively analysed the SAD usage on a general hematology ward (n=42) and SCT-unit (n=158) within our department. Pt characteristics, organ function, SE, PDI, treatment outcome and costs were assessed. Data was obtained by daily participation on ward rounds, consultation of ward physicians and review of pts' medication charts. SAD were given according to EORTC-adapted guidelines, with fluconazole given as primary prophylaxis in allo-SCT recipients and posaconazole for AML/MDS pts under induction chemotherapy. Empirical therapy was implemented with liposomal amphotericin B (lip. AmphoB) or caspofungin, preemptive therapy and therapy of aspergillus infections with voriconazole, caspofungin or lip. AmphoB.

200 consecutive pts under SAD treatment showed pt characteristics as displayed in Table 1, with leukemia (n=125) and lymphoma (n=51) as predominant diseases. Transplant (especially allo-SCT) pts were treated more frequently with intravenous (iv) SAD and with two or more consecutively applied SAD. Allo-SCT recipients received SAD earlier with higher pt numbers being treated prophylactically and empirically. The mortality rate due to fungal infections was significantly higher in allo-SCT recipients compared to other subgroups. The median duration of SAD use was considerably longer and median SAD costs exceeded those of auto-SCT and non-transplant pts (Table 1).

Lip. AmphoB was primarily applied as empirical therapy and showed an unfavorable safety profile with more SE (predominantly nephrotoxicity) and PDI compared to other SAD (Table 2). Voriconazole (mainly applied as preemptive therapy) and posaconazole displayed hepatotoxicity and numerous pharmacokinetic PDI, whereas caspofungin showed a favorable safety profile, with least SE and PDI. The echinocandin was primarily applied as 2-line therapy, whereas all other SAD were commonly given as 1-line therapy.

Earlier onset and longer duration of SAD as well as their increased i.v.-use lead to substantial costs among allo-SCT pts who are at high risk of developing invasive mycoses. SE and PDI frequently arise from the use of lip. AmphoB, whereas caspofungin appears to be well-tolerated. Our detection of frequent SE and PDI with SAD as well as the cost analysis should help us to avoid application errors, thereby enhancing pts' safety, and to assure economically appropriate SAD use. Enrollment of additional pts is ongoing, which will be presented at the meeting.

Neubauer:MSD Merck Sharp & Dohme GmbH: Research Funding. Engelhardt:MSD Merck Sharp & Dohme GmbH: Research Funding.