Dose Escalation of Caspofungin for Invasive Aspergillosis - A Phase II Trial
Abstract Abstract 2309 Objectives. Treatment of invasive aspergillosis (IA) fails in up to 50% of all cases and the mortality rate is at least 30%. Antifungal combination treatment has not been proven to be beneficial and dose escalation with liposomal amphotericin B did not improve outcome. New approaches are needed for patients with severe immunosuppression. Methods. Escalating high dosages of caspofungin were investigated in IA defined according to modified EORTC/MSG criteria. The tested cohort of patients received 70mg, 100mg, 150mg or 200mg QD, 8 patients each were to receive caspofungin first-line treatment for proven/probable IA for up to 28 days. Dose limiting toxicity was defined a…
Phase II dose escalation study of caspofungin for invasive Aspergillosis.
ABSTRACT Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics w…
Future challenges and chances in the diagnosis and management of invasive mould infections in cancer patients
Abstract Diagnosis, treatment, and management of invasive mould infections (IMI) are challenged by several risk factors, including local epidemiological characteristics, the emergence of fungal resistance and the innate resistance of emerging pathogens, the use of new immunosuppressants, as well as off-target effects of new oncological drugs. The presence of specific host genetic variants and the patient's immune system status may also influence the establishment of an IMI and the outcome of its therapy. Immunological components can thus be expected to play a pivotal role not only in the risk assessment and diagnosis, but also in the treatment of IMI. Cytokines could improve the reliability…